a hospital for all mankind': clinical investigation at the hospital of the rockefeller medical...

GBR/ Rockefeller Hospital/ 4/22/15

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‘A HOSPITAL FOR MANKIND’:

CLINICAL INVESTIGATION AT THE HOSPITAL OF

THE ROCKEFELLER MEDICAL INSTITUTE

Updated and expanded paper originally presented at the conference on 20th

century biomedical science sponsored by the National Institutes of Health

December 2005

“Programs of the large research foundations imply the hope that by such endowments new facts and new points

of view fundamentally important in medicine may be discovered. Many of these establishments serve in a way to mediate between the problems of practice and the

findings of science.”(1912) 1

ABSTRACT Translating biological knowledge from the laboratory to the bedside as well as collecting clinical data to stimulate further bench research remain at the core of Western medicine’s advances. This inquiry probes the historical evolution of clinical investigation in hospitals employing a multilevel framework that highlights the overlapping boundaries of space, social structure, professional status, scientific knowledge, human values, and moral sensitivity. Using the example of New York’s Rockefeller Research Institute and Hospital during the early 1900s, the essay explores how conditions necessary for conducting bedside studies were negotiated and implemented. The creation of a new clinical research mission, training of physician/scientists, as well as the establishment of a novel patient/researcher relationship laid the foundations for modern American biomedicine.

1 Editorial, “The Medical Man and Research,” Journal of the American Medical Association 59 (Aug 24, 1912); 655.


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Introduction

Among the fundamental challenges facing America’s clinical investigation

today is the persistent gap between the extraordinary advances in biomedical

knowledge that occurred in the past decades and their application to human

health and disease.2 Some mourn this estrangement between the laboratory and

the bedside, calling for a rapprochement by invoking the spirit that prevailed a

century ago at the Rockefeller Institute for Medical Research and its hospital in

New York. “Lost in Translation” is the phrase commonly employed. Among the

problems cited is the ever-shrinking amount of time for investigation in the face

of financial solvency and an “explosive” demand for medical care. These factors

make it more difficult to recruit, mentor and retain a critical number of full-

time clinical scientists, leading to a paucity of translators.3 On the other side,

there are also difficulties in recruiting human subjects for trials. The older bonds

of altruism and trust have given way to patient rights, detailed risk assessments

and informed consent.4 To make matters worse, bureaucracy is often clogging

the pipeline. Lack of oversight leaves matters in the hands of the pharmaceutical

industry.

Given such obstacles, a new discipline, “translational medicine,” has

emerged to close the “bench-to-bedside” interlude, covering not only the

2 Nancy S, Sung et al., “Central Challenges Facing the National Clinical Research Enterprise,” JAMA 289 (Mar 12, 2003): 1278-87. 3 L.E. Rosenberg, “The Physician-Scientist: An Essential and Fragile Link in the Medical Research Chain,” Journal of Clinical Investigation 103 (Jun 1999): 1621-1626. 4 Jeffrey M. Drazen, “Patients at Risk.” New England Journal of Medicine 353 (Jul 28, 2005): 417.


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“effective translation of biomedical discoveries for prevention, diagnosis and

treatment”, but also eliminating the breach between new medical experiences

and average clinical and public health practices.5 As a result, “re-engineering the

clinical enterprise” has become a prominent theme within the recent National

Institutes of Health Roadmap for Medical Research.6 “ We strive to remain—

collectively—the best clinical research enterprise in the world,” proclaimed Elias

Zerhouni, Director of the NIH.7 In a society intimately wedded to the automobile,

the use of such metaphors is not surprising. Roadmaps have become fashionable;

they imply the creation of templates for strategic planning, directions, and

attainable goals.8

Probing the historical evolution of clinical investigation in American

hospitals during the first half of the 20th century can contribute to such a guide. .

Little has been written about the reciprocal process of “translating”—that is to

say reinterpreting and reformulating-- knowledge from one evidentiary context,

the laboratory, to another one at the bedside, then back to the laboratory

generating new lines of investigation. Because of its diversity and complexity,

the topic has been subjected to a number of diverse approaches. Some studies

have closely focused on the experiments themselves, their shifting methodology,

5 Steven H. Woolf, “The Meaning of Translational Research and Why it Matters,” JAMA 299 (Jan 2008): 211-13. 6 Elias Zerhouni, “The NIH Roadmap,” Science 302 (3 Oct 2003): 63-4 and 72. 7 Elias A. Zerhouni, “Translational and Clinical Science--Time for a New Vision,” New England Journal of Medicine 353 (Oct 13, 2005): 1621-3. 8 G. Ryan et.al, “Reengineering the Clinical Research Enterprise to Involve More Community Clinicians, “ Implementation Science 6 (2011): 36 http://www.implementationscience.com


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subjects and ethics. Others have called for a broader view of the policies driving

human-based research by examining the relationships between government and

medical science. There is also a plethora of “human guinea pig” horror stories,

led by Nazi Germany’s experiments, 9 exposing the actions of callous or

overzealous researchers and the harm caused to their vulnerable and uninformed

subjects.10

In recent times, the history of informed consent has become a convenient

framework for exposing some of the ambiguities of the researcher/patient

relationship.11 Before arriving at any judgments of past performances, however,

it is imperative that we carefully examine the historical contexts for a better

understanding the values and moral standpoints involved. Not only ethicists but

also professional historians are not immune to the tendency of judging the past

according to contemporary standards. No easy analogies between past and

present will due. By restricting the inquiry to hospitals, however, there is an

additional problem: in addition to being imbedded in larger political and cultural

contexts, institutions possess their own “ecologies,”—even personalities--value

systems and financial priorities that differ from the ideals of individual medical

9 See Paul J. Weindling, Nazi Medicine and the Nuremberg Trials: From Medical War Crimes to Informed Consent, New York: Palgrave Macmillan, 2005. 10 Jochen Vollmann and Rolf Winau, “Informed Consent in Human Experimentation Before the Nuremberg Code,’ British Medical Journal 313 (Dec 7, 1996): 1445-1447. For more information, Susan E. Lederer, Subjected to Science: Human Experimentation in America Before the Second World War, Baltimore: Johns Hopkins University Press, 1995. 11 Tom L. Beauchamp and Ruth R. Faden, “History of Informed Consent,” in Encyclopedia of Bioethics, rev. ed., ed. Walter T. Reich, New York: Simon & Schuster Macmillan, 1993, vol.3, pp. 1232-1238. A more recent synthesis is Robert Baker, “American Research Ethics, 1800-1945,” in Before Bioethics: A History of American Medical Ethics From the Colonial Period to the Bioethics Revolution, New York: Oxford University Press, 2013, pp. 232-273.


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encounters between physicians and patients.12

Historians have recently suggested a new form of analysis: the

“biomedical platform,” a configuration of values, discourses and institutional

programs, space, personnel and equipment, all assembled for the purpose of

melding biology with medicine. Such a broader and flexible construct has the

advantage of organizing the dynamics of translational research between bench

and bedside within a wider lens subject to historical contingency.13 The approach

echoes in part Foucault’s notion of “dispositif,” a network of philosophical

propositions, discourses, scientific statements as well as institutions, their

spatial arrangements and administrative rules.14 In hospitals, this discursive and

material process allows for the integration of infrastructure such as architectural

features, equipment, and administration, with scientific rationales, laboratory

research, standardized routines, medical and nursing care, and improved record

keeping. Moreover, new funding sources, technological advances and a novel

type of patients--individuals willing to be subjected to scientific scrutiny--are

involved.

The call for such integrated approaches must acknowledge the importance

of models based on local institutional contexts. Since their inception, Western

12 See, for example, James G. Haughton, “Determinants of the Culture and Personality of Institutions,” in Integrity in Health Care Institutions: Humane Environments for Teaching, Inquiry and Healing, eds. E.E. Bulger and S.J. Reiser, Iowa City: Univ. of Iowa Press, 1990, and S.L. Star and J.R. Griesemer, “Institutional Ecology: Translation and Boundary, Social Studies of Science 19 (1989): 367-420. 13 Peter Keating, Biomedical Platforms: Realigning the Normal With the Pathological in Late Twentieth-Century Medicine, Cambridge, Mass.: MIT Press, 2003. 14 The term refers to institutional, physical and administrative knowledge structures sustaining power within society. Michel Foucault, “The Confessions of the Flesh” (1977) interview, in Power/Knowledge, Selected Interviews and Other Writings, ed. Colin Gordon, 1980, pp. 194-228.


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hospitals have played a number of important roles in society. They were initially

instruments of religion, welfare and, segregation.15 Less known is their function

as key sites for translational research--predominantly the testing of drugs--since

at least the 15th century, although recently this role is diminishing as outpatient

venues become popular.16 An early twentieth-century review stressed the notion

that “hospitals always have been and always must be, from the very nature of

things, the great means of advancing medical knowledge.”17 Indeed, as

traditional welfare institutions, they harbored a large number of disabled and

sick people. Inmates were carefully chosen and subjected to a regimented

institutional life that controlled their institutional lives.

Since medical knowledge has historically been constructed on the basis of

information and behavior displayed by sick individuals, hospital patients provided

favorable opportunities to assess the nature of disease and therapeutic results.

Therefore, Western medical knowledge obtained during recent centuries, derives

mostly from the distinct behavior exhibited by hospital populations. Bedside

observations were responsible for the creation of new disease classifications;18

dissections contributed to the advancement of pathological anatomy, and

15 For a broader view, Guenter B. Risse, Mending Bodies, Saving Souls: A History of Hospitals, New York: Oxford University Press, 1999. 16 Harry M. Marks, The Progress of Experiment: Science and Therapeutic Reform in the United States, 1900-1990, New York: Cambridge University Press, 1997. 17 Michael Foster, “The Scientific Use of Hospitals,” in The Nineteenth Century and After 49 (1901): 57. 18 Stephen J. Kunitz, “Classifications in Medicine,” in Grand Rounds: One Hundred Years of Internal Medicine, eds. Russsell C. Maulitz and Diana E. Long, Philadelphia: University of Pennsylvania Press, 1988, pp. 279-296.


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comparative drug treatments disclosed their pharmacological value. Hospital

laboratories, for their part, contributed decisively to quantify and measure

clinical and pathological phenomena. 19 Today, these practices continue to raise

profound epistemological and ethical consequences for medicine.20

My intent, therefore, is to place clinical experimentation in hospitals

within a multilevel, ecological framework, highlighting the overlapping

boundaries of space, social structure and class, professional status, scientific

knowledge, human values and moral sensitivity.21 The working hypothesis guiding

this study is that the conditions necessary for conducting clinical research in

hospitals were gradually negotiated within shifting institutional and ethical

guidelines, leading to the creation of a new patient/researcher relationship.

Instead of the usually coerced and institutionally powerless masses, the inquiry

features a particular class of experimental subjects: individuals eager to

voluntarily participate in such studies. Although discredited by many, particular

examples can still be useful in teasing out the complex web of factors operating

19 J. Buttner, “Impacts of Laboratory Methodology on Medical Thinking in the 19th Century,” Clin. Chem. Lab. Med 38 (Jan 2000): 57-63. See also V. Hess, “Standardizing Body Temperature: Quantification in Hospitals and Daily Life,” in Body Counts: Medical Quantification in Historical and Sociological Perspectives, eds. G. Jorland, A. Opinel and G. Weisz, Montreal: McGill/Queens Univ. Press, 2005, pp. 109-126. 20 Daniel Callahan, What Price Better Health? Hazards of the Research Imperative, Berkeley: Univ. of California Press and Milbank Memorial Fund, 2003. 21 Paul Starr, “The Reconstitution of the Hospital,” in The Social Transformation of American Medicine, New Yoke, Basic Books, 1982, pp.145-179.


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in clinical investigation. A case study dealing with the genesis and early years of

the Rockefeller Hospital follows.22

Constructing a Clinical Research Mission23

Both the Rockefeller Institute for Medical Research and Hospital were the

brainchildren of the Reverend Frederick T. Gates, a Baptist minister. Gates

became the principal adviser to John D. Rockefeller, Sr., conducting both his

business affairs and philanthropic endeavors. Prompted by friends--including a

medical student--Gates perused William Osler’s recent Principles and Practice of

Medicine in the summer of 1897, a popular textbook reflecting recent advances

in medical science.24 Impressed but also mindful of the humanitarian and

economical possibilities of modern medicine, he attempted to persuade his

employer to channel his philanthropic efforts into this field.25 The decision to

22 A. McGehee Harvey, “The Development of the Rockefeller Institute for Medical Research and its Hospital,” in Science at the Bedside: Clinical Research in American Medicine 1905-1945, Baltimore: Johns Hopkins University Press, 1981, pp. 78-100. 23 I am indebted to the careful reconstruction based on surviving archival materials by Olga Amsterdamska, “Research at the Hospital of the Rockefeller Institute for Medical Research,” in Creating a Tradition of Biomedical Research: Contributions to the History of The Rockefeller University, ed. David H. Stapleton, New York: The Rockefeller University Press, 2004, pp. 111-126. 24 William Osler, The Principles and Practice of Medicine, New York: D. Appleton & Co., 1892. For an introduction to this work, see Osler’s Textbook Revisited, eds. A. McGhee Harvey and Victor A. McKusick, New York: Appleton Century Crofts, 1967. 25 See “Gates and Medicine, “ in Howard Berliner, A System of Scientific Medicine: Philanthropic Foundations in the Flexner Era, New York: Tavistock, 1985, pp. 76-01, and Frederick T. Gates, Chapters in My Life, New York: 1977. Paul H. de Kruif who worked briefly at the Institute observed: “rich men who set up laboratories out of altruistic or other motives, deserve to be pardoned by their less fortunate and consequently envious countrymen who denounce them as commercial brigands.” See his Our Medicine Men, New York, The Century Co, 1922, p. 46. For an unflattering portrait of American philanthropy, E. Richard Brown, Rockefeller Medicine Men: Medicine and Capitalism in America, Berkeley, University of California Press, 1979.


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proceed--possibly influenced by the recent death of Rockefeller’s grandson from

scarlet fever--lead to the incorporation of the Institute for Medical Research in

1901 based on an initial gift of $200,000 dollars.26 As a member of the Board of

Trustees and Board of Scientific Directors from 1901 to 1930, William H. Welch,

the distinguished pathologist from Johns Hopkins, played a key role in the

genesis and development of both the Institute and its hospital.27 The latter was

conceived as a useful adjunct for testing the Institute’s discoveries. Welch

believed that medicine was “destined to play a leading part in the solution of

many of the industrial, economic and social problems of the world.”28

Since the beginning of the twentieth century and even earlier, American

medical leaders strongly endorsed a philosophical commitment to science.

Health, broadly conceived, was essential for human progress and civilization,

disease the root of all evil. William Osler at the Johns Hopkins Hospital in

Baltimore shared the European enthusiasm for laboratory science and its

application in clinical medicine.29 However, Osler’s notion of the hospital as an

experimental space merely highlighted the importance of diagnostic accuracy

26 An excellent summary of the first two decades was provided by Simon Flexner, “The Rockefeller Institute For Medical Research, New York,” in Forschungsinstitute: ihre Geschichte, Organisation and Ziele, ed. L. Brauer, 2 vols. Hamburg: P. Hartung, 1930, vol. 2, pp. 458-480. 27 For a detailed portrait of Welch’s (1850-1934) career in the context of contemporary developments in American medicine, see Simon Flexner and James T. Flexner, William Henry Welch and the Heroic Age of American Medicine, New York: Viking Press, 1941, especially ‘The Rockefeller Institute for Medical Research,” pp. 269-296, and “Science at the Bedside,” pp. 297-328. 28 William H. Welch, “The Hospital in Relation to Medical Science,” Journal of the American Medical Association 59 (1912): 1668. 29 The literature about William Osler is quite extensive. For a more recent biography see Michael Bliss, A Life in Medicine, New York: Oxford University Press, 1999. An earlier and more extensive biography is Harvey Cushing, The Life of Sir William Osler, 2 vols. Oxford: Clarendon Press,1925.


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while adhering to the earlier tenets of therapeutic skepticism. With the help of

clinical laboratory facilities, physicians could now also explore the impact of

diseases on human physiology and pathology, especially those of an infectious

nature that could be identified by bacteriology. In his Aphorisms, Osler insisted

that the goal was to make the hospital a place where the medical art could be

practiced based on scientific principles.30

By 1902, Simon Flexner, a protégé and former student of Welch who would

soon assume the directorship of the Rockefeller Institute, held similar notions.

Although in possession of a medical degree from a two-year proprietary school,

Flexner had never practiced. He was a true “laboratory man,” trained as a

pathologist at Hopkins with interests in the epidemiology and pathogenesis of

infectious diseases. Appointed Professor of Pathology at the University of

Pennsylvania in 1900, Flexner also assumed the directorship of the Clinical

Laboratory at the University’s teaching hospital. Based on the successes of Emil

Behring’s diphtheria’s antitoxin, he was keenly interested in finding “germicidal

substances”--vaccines or sera--that would protect people from the onslaught of

certain infectious diseases or diminish their clinical impact. In addition to

spurring the proliferation of white blood cells, such “antibodies” would clump

the offending microorganisms and neutralizing possible endotoxins. Flexner’s

interests in bacteriology led to his involvement with outbreaks of cerebrospinal

30 Sir William Osler’s Aphorisms From His Bedside Teachings and Writings, collected by Robert B. Bean, ed. by William B. Bean, New York: H. Schuman, 1950.


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meningitis in Maryland and bubonic plague in San Francisco.31 Given his training

and epidemiological exposure, he was considered a perfect choice for the

Rockefeller Institute post. The original charter demanded that the Institute

“conduct, assist and encourage investigations in the sciences and arts of hygiene,

medicine and surgery, and allied subjects,” This included the nature and causes

of disease as well as the methods for its prevention and treatment. Furthermore,

newly acquired knowledge would be made available “for the protection of the

health of the public and the improved treatment of disease and injury.”32 As

expected, Flexner vowed that the new institution would never neglect the

immediate problems of human disease.33

Two years later, on October 15, 1904, the first Rockefeller-financed

laboratory opened in temporary facilities leased from the New York City Nursery

and Child Hospital on East 50th St while construction of a new, high-rise building

proceeded on a 13-acre track of land purchased by the Rockefellers. The parcel

was located on Manhattan’s Upper East Side, overlooking the East River at 66th

Street and York Ave. Even before formerly opening its doors on May 11, 1906 at

its permanent location, the lofty goals established for the Institute for Medical

Research were already being fulfilled during the 1905 epidemic of cerebrospinal

meningitis in New York City. Confronted with about 4,000 patients and a 31 For the latter, see Guenter B. Risse, “Expert Opinion: Adventures of a Federal Commission,” in Plague, Fear, and Politics in San Francisco’s Chinatown, Baltimore: Johns Hopkins University Press, 2012, pp. 167-174. 32 The Rockefeller Institute of Medical Research: History, Organization and Equipment, New York: Rockefeller Institute, 1912, p. 5. See also Harvey, Development, pp. 78-100. 33 Jules Hirsch, “The Role of Clinical Investigation in Medicine: Historical Perspective From the Rockefeller University,” Perspectives in Biology and Medicine 41 (1997): 108-117.


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mortality of 75%, Flexner successfully proposed a much more effective

intraspinal route for the administration of the protective horse serum to the seat

of this disease, thus saving lives. Although ‘Flexner’s serum’ was not original--

this approach had been used by the New York Health Board’s William H. Park--

newspaper revelations and freely distributed samples by the Institute cemented

the Director’s reputation as a leading scientist and protector.34

Yet, while the Research Institute flourished, Rockefeller Sr. hesitated to

provide additional funding for the planned hospital, another display of his

traditional philanthropic prudence. In an early 1901 report, the Scientific Board

of Directors had already recommended that the focus of medical investigation

address the “threatening dangers” posed by infectious diseases in “our present

social system.”35 Now, six years later, Flexner pleaded with the Board of

Trustees, emphasizing that “in a hospital affiliated with the Institute, patients

could be studied with an unprecedented degree of thoroughness,” an approach

that stood in sharp contrast with conditions prevailing at other contemporary

New York institutions. Welch, his Hopkins mentor, agreed, stressing the promise

of diagnostic improvements. “The hospital,” he declared in a 1907 speech, “is

the laboratory where the results of nature’s experiments are to be studied and

alleviated by the methods of science.” Welch went on to say, “It is increasingly

clear that the scientific study of the problems of disease can be undertaken with

34 Corner, A History, pp. 59-62. 35 The report is cited in Amsterdamska, Creating a Tradition of Biomedical Research, p. 113.


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the greatest advantage in well-equipped, special laboratories connected with the

hospital clinics.”36

Part of the impetus for establishing a hospital served as a reminder that the

mission of the new investigative enterprise aimed towards improving the chances

of sick people to recover. There was also growing agreement that the hospital

bedside was the ideal testing place for “new thought” generated in affiliated

research institutions. This was already happening at the Koch Institute in Berlin

and Pasteur Institute in Paris. Under the circumstances, the Board dominated by

Welch and Flexner wished to tightly control the translations from bench to

bedside, rejecting in 1906 a potential affiliation with New York’s Presbyterian

Hospital. Public relations were equally important: a new hospital would further

spotlight the charitable impulses guiding Rockefeller’s benevolent endeavors.

When John D. Rockefeller Jr. finally announced in May 1908 that his father

had pledged an additional sum of $500,000 dollars for the construction of a

hospital to be linked to the existing Institute for Medical Research, two goals

were stressed. The first was to emphasize that the new institution with its well-

equipped modern laboratories would be a destination for New Yorkers suffering

from unusual diseases requiring specialized study and care from clinicians

familiar with the most recent biomedical advances in diagnosis and treatment.

The second objective was to provide facilities where remedies discovered by

Institute investigators could be tried and evaluated. These treatments were to

be directed at sufferers of diseases currently regarded as “chief scourges of 36 William H. Welch, “The Relation of the Hospital to Medical Education and Research,” Journal of the American Medical Association 49 (1907): 532.


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mankind.”37 Rockefeller Jr. cited Simon Flexner’s experimental serum for the

treatment of cerebrospinal meningitis as a prime example.38 Indeed, the

donation was framed “in grateful recognition” for Flexner’s therapeutic

successes a year earlier during an epidemic of this disease in Ohio that managed

to reduce mortality by nearly 50%.39 Flexner himself acknowledged that his

experimental serum was already being successfully tested all over the world.

Asked about the terms of this bequest, Simon Flexner was quoted by the

New York Times that not only would the hospital treat certain obscure diseases

but also common ones where cures still remained elusive. Among them was

“infantile paralysis” or better poliomyelitis, an often-lethal disease of young

children that had recently acquired epidemic proportions nationwide. Polio’s

summertime impact in New York City since 1907 drew the attention of Flexner

and the local Neurological Society.40 To justify forthcoming experimental clinical

endeavors, Flexner cautioned that all trials on patients would be preceded by

animal tests to reduce risks. His key message, repeatedly delivered to the public,

was that the new Rockefeller Hospital would be of great service to medicine and

patients because its staff would ascertain and develop new and better methods

37 The Rockefeller Institute of Medical Research: History, Organization and Equipment, p. 10. 38 NY Times, May 31, 1908. By 1911, The Rockefeller Institute claimed that its use had reduced the mortality from this disease by about 70%. NY Times, Feb 13, 1911. 39 Letter from John D. Rockefeller to L. Emmet Holt, May 28, 1908, cited in George W. Corner, A History of the Rockefeller Institute, 1901-1953; Origins and Growth, New York: Rockefeller Institute Press, 1964, p. 61. 40 Saul Benison, “Speculation and Experimentalism in Early Poliomyelitis Research,” Clio Medica 10 (1975): 1-22.


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of diagnosis and cure.41 Moreover, new treatments based on experimentally

derived principles obtained from the blood of animals would “become a matter

of certainty.”42

Details of the collective process that eventually led to the establishment

of this unique institution shed additional light on its mission. Besides Welch and

Flexner, Christian A. Herter, a close Rockefeller acquaintance and prospective

Hospital director, together with Rufus Cole, who eventually succeeded him, all

contributed their own, somewhat divergent visions of the project.43 In 1907,

Herter, another Welch student and renowned biochemist, expressed the notion

that hospital research and patient care should be combined but function

separately. Herter himself and a staff of scientists would carry out the former,

while treatments and caregiving remained the responsibility of house physicians

providing routine, around the clock services. The intent was to bridge the

prevailing realities of mutual distrust and contempt between “old docs” and

young “lab men.”44 Herter’s two-tiered scheme envisioned residents working

under the supervision of attending practitioners drawn from the ranks of 41 For details, John R. Paul, A History of Poliomyelitis, New Haven: Yale University Press, 1971, especially pp. 98-125, 42 For an overview, J. Rosser Matthews, Quantification and the Quest for Medical Certainty, Princeton, NJ: Princeton University Press, 1995. 43 Christian A. Herter was Professor of Pathological Chemistry at the Bellevue Hospital Medical College. He owned a private laboratory in the city, studying infantilism, intestinal infections, and autointoxication. For details of his life and career, R.M. Hawthorne, Jr., “Christian Archibald Herter MD (1865-1910),” Perspectives in Biology and Medicine 18 (1974): 24-39. A collection of Herter’s papers can be found at the Alan M. Chesney Medical Archives, Johns Hopkins Medical Institutions. 44 Gerald L. Geison, “Divided We Stand: Physiologists and Clinicians in the American Context,” in The Therapeutic Revolution: Essays in the Social History of American Medicine, ed. Charles E. Rosenberg, Philadelphia: University of Pennsylvania Press, 1979, pp. 67-90.


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prominent New York clinicians allowed to retain their private practices. Going

beyond Flexner’s plan, however, Herter expanded the scope of clinical research,

insisting that the hospital’s physician in chief (Herter) needed his own research

space and professional staff in conjunction with several clinical laboratories for

routine testing.45

Even before Herter’s tragic death, Cole, appointed as the first hospital

director in November 1908, responded to a query from Welch and Rockefeller

Institute directors. Welch wanted to know from Cole whether he believed that

the work of the Rockefeller Hospital would promote the Institute’s scientific

activities or function independently. Cole, a Hopkins graduate and resident who

had trained under Osler, was a “new doc” who believed that to really understand

disease and to perfect rational measures of treatment, more refined methods of

investigation were required.46 They included experimental studies designed to

disclose the etiology and biological mechanisms of the most common diseases.47

In charge of Hopkins’ Biological Division of the Clinical Research Laboratory, Cole

proceeded to lay out his own vision in a letter to Flexner. He was emphatic in his

belief that the applied role of the clinical institution articulated by the

Rockefellers, Flexner, and Herter, should be transcended. In Cole’s opinion, the

45 Amsterdamska, Research at the Hospital, pp. 115-117. 46 For a brief biography of Rufus Cole (18722-1966) by C. Phillip Miller see Addresses Made at a Dinner in Honor of Dr. Cole on the Occasion of his Retirement as Director of the Hospital, New York: Rockefeller Institute of Medical Research, 1938, pp. 119-129. An obituary appeared in the NY Times, Apr 22, 1966. 47 Rufus Cole, “Hospital and Laboratory,” Science 66 (Dec 9, 1927): 545-552. Cole’s investigations centered on the study of pneumonia--then a common and lethal disease--and the biology of various pneumococcus strains.


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physical and intellectual barriers between the bedside and laboratory common in

most hospitals had seriously delayed the advancement of American medicine. He

wanted to create a hospital environment free from ordinary routines of practice

and teaching. Clinical work was to be a full-fledged partner, not a handmaiden

of medical research.48

The new Rockefeller Hospital was thus conceived as an independent but

closely affiliated department of the Research Institute, to be populated with

clinicians with advanced laboratory training and experience. Cole explained that

the Hospital should “extend the field of the Research Institute’s research so as to

include the study of disease in its clinical aspects, under conditions as near as

possible to standards of laboratory exactness and efficiency.”49 Placed in such a

clinical milieu, investigators would reduce the problems of pathology to

biological puzzles, laying the groundwork for additional laboratory research that

could, in turn, yield answers designed to improve the diagnosis and management

of important diseases. For its time, Cole’s translational approach seemed truly

revolutionary. However, his plea for scientific cross-fertilization required a

momentous intellectual and organizational shift based on intellectual parity and

close personal collaboration. In Cole’s proposed scheme, the burgeoning clinical

laboratories currently providing measurements of bodily functions and

bacteriological diagnoses would significantly expand their functions and

48 For details, Jules Hirsch, “Rufus Cole and the Clinical Approach,” in Creating a Tradition of Biomedical Research, pp. 127-134. 49 Minutes of the Board of Directors, Jan 12, 1907, cited in Corner, A History, p. 90.


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importance, becoming independent instruments for new inquiries into the

biological foundations of human pathology.50

In spite of his appointment to head the Rockefeller Hospital, Rufus Cole’s

collaborative vision continued to be tested by Flexner and the Institute’s

Scientific Board. Flexner, ever the strict laboratory experimentalist, still viewed

the activity of clinicians as evolving in a distinct and separate sphere, a view

that surfaced during the 1911 polio epidemic. For Flexner, “the value of the

laboratory lies in its ability to supply certain definite facts about which there can

be no doubt or misunderstanding,” he wrote in 1901. Laboratory errors, “even

under the worst conditions” remained “small compared with most clinical

observations.”51 Cole, for his part, kept insisting that clinicians who were

studying disease had the right to go as deeply into its fundamental nature as

their training allowed. He indicated that after “some effort and energy” he had

persuaded them to adopt his approach, hoping that these young men would

contribute to the “revolution or evolution of clinical medicine bound to come.”

To gain the respect of their colleagues, however, hospital researchers first

needed to accomplish “something independently.” Spontaneous cooperation with

Institute scientists was more desirable and would surely follow. 52

50 Rufus Cole, “The Inter-Relation of the Medical Sciences,” Science 67 (1928): 47-52. 51 S. Flexner, “The Clinical Laboratory in Surgical Diagnosis,” NY State Journal of Medicine 3 (1901): 353, as quoted in Ross, “Making Medicine Scientific, p. 217. 52 Much has been written about this subject. The most balanced and recent analysis based on original research is Karen Deanne Ross, “Making Medicine Scientific: Simon Flexner and Experimental Medicine at the Rockefeller Institute for Medical Research, 1901-1945”, Ph.D. dissertation, University of Minnesota, 2006.


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Designing a New Research-oriented Hospital

In the early 1900s, the United States was in the midst of a veritable

countrywide hospital construction boom. Located mostly in urban areas, these

institutions allowed members of the affluent class to leave their homes with the

expectation of superior care. The lure was comfort and privacy, improved

nursing and medical expertise. 53 The linkage of research and care proposed by

Rufus Cole required new spatial arrangements. Between February 1909 and its

completion in October 1910, the new director and the Rockefeller Board of

Scientific Directors engaged in a series of negotiations with architects and

patrons about fully funding, designing, and building the new hospital.54

For the laboratory bench and hospital bed to become closer neighbors,

however, modern hospital architecture had to reorganize the distribution of

wards and make room for research laboratories and other diagnostic equipment.

Today, we still fail to fully appreciate the critical importance of designing

particular physical plants and how, following construction, they influence the

range of activities planned for a particular institution.55 By the early 1900s, there

53 See Albert J. Ochner and J. Sturm Meyer, The Organization, Construction and Management of Hospitals, With Numerous Plans and Details, Chicago: Cleveland Press, 1909. 54 For a detailed account based on the original correspondence, Olga Amsterdamska, “Research at the Hospital of the Rockefeller Institute for Medical Research,” in Creating a Tradition of Biomedical Research, pp. 111-126. 55 Edward F. Stevens, Edward P, Casey, and Clarence W. Williams, Modern Hospitals. A Series of Authoritative Articles on Planning, Details, and Equipment As Exemplified by the Best Practice in this Country and Europe, New York: The American Architect, 1914. For a recent analysis, Annmarie Adams, Medicine By Design: The Architect and the Modern Hospital, 1893-1943, Minneapolis: University of Minnesota Press, 2008.


20

was a mounting consensus that hospitals had to be reorganized on the basis of

industrial principles that placed a premium on the analysis and division of labor.

Like factory work, medical tasks needed to be streamlined and standardized,

with patients and caregivers becoming cogs in a “production line” extending

from admission to discharge.56

Hospital design and construction responded to new forms of institutional

organization and management. Good planning and economical construction

would reduce future maintenance costs. Planners, however, were acutely aware

of the ever-shifting requirements and technological hardware, always trying to

anticipate future needs. They often feared that philanthropists, interested in

sponsoring new institutions but not directly involved with their subsequent

operations, would insist in erecting attractive and expensive buildings as

monuments to their charitable intentions.57 After his appointment as director of

the Rockefeller Hospital, Rufus Cole went abroad in the fall of 1908 to visit a

number of medical institutions in Germany and gather ideas about how to

organize clinical research. His final plans were summarized in a November

memorandum presented to the Board of Trustees. After further negotiations,

several design changes and cost overruns—Cole threatened to resign over them--

56 Allan M. Brandt and David C. Sloane, “Of Beds and Benches: Building the Modern American Hospital, in The Architecture of Science, eds. P. Galison and E. Thompson, Cambridge, Mass.: MIT Press, pp. 281-305. In my time as a resident in the early 1960s, Henry Ford Hospital in Detroit, Michigan, was compared to an assembly line “stamping out disease.” 57 See details, Edward F. Stevens, The American Hospital in the Twentieth Century, New York: Architectural Record Publ. Co., 1918.


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the result was—in the words of a trustee—a strictly utilitarian structure with

limited space and expenditure.

The site chosen for the hospital building was located on Manhattan’s

Upper East Side bluff originally purchased by Rockefeller at the foot of 66th St

between York Ave. and the East River, south and adjacent to the existing

Research Institute. The prestigious New York architectural firm of York and

Sawyer developed the preliminary plans.58 A member of the American Institute of

Architects since 1902, Edward P. York was designing some of the largest buildings

in the city, specializing in neoclassical structures including banks and hospitals.

His selection for this project owed much to his expertise and reputation, as well

as his earlier training at the Boston architectural firm of McKim, Mead and White

that had built the Research Institute.59

The proposed hospital was to be a single rectangular-shaped high-rise

structure built of steel, concrete, limestone and brick. Overlooking the East

River, the institution’s major axis ran in a west-east direction, exposing its

southern front and sides to ample sunlight. The building featured eleven floors,

three of them underground, the other four devoted to patients with a capacity of

over 50 beds.60 The structure had two elevators, one for patients, and the other

58 See A Brief History, Office of York & Sawyer, Architects, and a List of its Work, 1948, New York Public Library, Research Library. The firm had previous contacts with John D. Rockefeller regarding the buildings at Vassar College as well as several bank designs in New York City. 59 Edward Palmer York’s biographical sketch can be found among American Architects’ Biographies. An announcement from York & Sawyer about filing their plans appeared in The Brickbuilder 17 (Sep 1908): 220. 60 For contemporary debates about high-rise establishments, S.W. Lambert, “ Is Pavilion of Sky-scraper Hospital Best? Comparisons of Two Types and Arguments in Favor of the High Hospital in Crowded Cities,” Modern Hospital 1 (1913/1914): 95-98.


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for freight that could be reached from a central corridor. An additional

dumbwaiter connected the kitchen with all floors. The stairways were equipped

with fireproof screens and doors at every floor. Starting with the sub basement,

the establishment offered space for coal storage, a carpenter shop, water

reservoir tanks, elevator machinery, sterilizing and heating equipment. There

were also linen stores and laundry facilities, as well as servant bedrooms,

mending and sewing facilities, and an autopsy room with an adjoining

pathological laboratory and refrigerator for the preservation of cadavers. The

basement, for its part, at the western end of the building, hosted a patient

examining room and dispensary that could be accessed through a sunken

driveway reserved for ambulances and private automobiles. A medical records

office, butcher shop, and vegetable storage room connected with a kitchen and

pantry attached to three separate dining rooms, a maids closet as well as

clothing rooms.61

The first floor offered a covered entrance to a ample vestibule leading to

a wide central corridor stretching from the Director’s and Head nurse offices and

reception room with a view of the East River to staff dining and sitting rooms on

the west end. The sitting room was outfitted with bookcases and served as a

library. Featured were also six separate bedrooms for resident physicians, each

with its private bathroom, together with a “history room” presumably planned

for housing institutional medical records and archives. The doctors’ quarters on

the first floor were especially attractive because of their broad river views and 61 The architectural plans and photographs of the Rockefeller Hospital were published in American Architect and Architecture 100 (Oct 11, 1911): 125-132.


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the dramatic silhouette of the recently completed cantilever Queensboro Bridge.

The second floor was solely devoted to the hospital’s Superintendent and

Assistant Superintendent as well as the nursing staff. Both officials had their own

bed and sitting rooms as well as private bathrooms. Together with dining and

sitting facilities, six additional bedrooms on this level were reserved for the

nurses, four devoted to night-shift caregivers.

The next four stories were devoted to patients, with the third floor

reserved for two double rooms and eight single private rooms with their own

baths. They also sponsored nurses’ stations and small clinical laboratories,

together with a sitting room and four balconies, some facing the East River. The

fourth, fifth, and sixth levels offered two six-bed wards at each side of the

building, connected to large balconies facing west and east that allowed

bedridden patients to be wheeled out and face the fresh air. Separate clinical

laboratory facilities, nurses’ room, and examination space completed the

arrangement. At the center of level 4, planners created a hydrotherapy facility,

a spa for light and vapor baths built at the suggestion of Simon Baruch, a

prominent local physician, proponent of public baths, and interested in their

medicinal value.62

The seventh floor was exclusively devoted to biomedical research. It

featured four large laboratories located on all four corners of the building. Two

at the west end were specialized workrooms for biological experiments; at the

62 The Rockefeller Institute of Medical Research: History, Organization and Equipment, pp. 13-16. For information concerning Baruch see Patricia Spain Ward, Simon Baruch: Rebel in the Ranks of Medicine, 1840-1921, Tuscaloosa, University of Alabama Press, 1994.


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eastern end the space was devoted to chemical studies. A separate facility

hosted a balanced Polaris cope for the analysis of sugars developed by Frederick

J. Bates.63 There were also animal quarters, offices, and space for janitorial

services. An interesting detail was the placement of laboratories on the south

side of this floor. At that time, medical investigators working with microscopic

specimens were annoyed at the inconsistency of their light sources in the

identification of their stained bacteria samples. Gas or electric light could lead

to potentially erroneous identifications. It was sometimes difficult to test the

diagnostic accuracy if the sky over Manhattan was clear or cloudy. Daylight under

clear skies provided the best background for this work, and reflectors were

developed to achieve a standardized light spectrum and achieve diagnostic

consistency.64

Finally, the eight and top floor spotlighted a small operating room only

“intended for occasional or emergency use” together with a sterilizing facility

equipped with foot-operated faucets installed on surgical hand basins, and a

linen room. In addition, a photographical laboratory with a darkroom possessed

special entrances designed to exclude direct light.65 A sheltered, all-weather

outdoor roof garden and a section with overhead trolleys to hang unused

63 Bates (1877-1958) was the internationally known developer of a sacccharimeter that carries his name. He headed of the Polarimetry section of the National Bureau of Standards. 64 Melvin Spencer, “Hospital Lighting,” The New York Architect 5 (1911): 113-7. The essay reproduced a number of official images of the Rockefeller Hospital previously published in the American Architect. 65 For contemporary views on outfitting a hospital, John A. Hornsby and Richard E. Schmidt, The Modern Hospital: Its Inspiration, Its Architecture, Its Equipment, Its Operation, Philadelphia: W.B. Saunders, 1913.


25

mattresses for ventilation and exposure to sunshine completed the building’s

features. Presumable for patient comfort, there was also a closet for warming

blankets. Proper natural ventilation was achieved through the placement of two

fireplaces on the inner wall of each patient ward equipped with separate

chimneys; the laboratories employed special fans to exhaust the air. From all

appearances, the nearly one-million-dollar Rockefeller Hospital amply complied

with contemporary standards of organization, equipment and safety.66

To the north, next to the hospital, a separate, two-story pavilion with

nine rooms separated by glass partitions was dubbed “germ proof” and

completely devoted to the admission of cases suffering from contagious diseases.

In addition to its own clinical laboratory, the basement offered special laundry

and sterilization equipment capable of dealing with the clothing and bedding of

infected patients. The building’s first floor featured nine single rooms with

private baths separated from each other by plate glass partitions. A reception

room, kitchen, pantry, and nurses’ station were placed across a central corridor

facing the patients. The second story was devoted entirely to the housing of

nurses attending contagious patients, a place for temporary sequestration

although these caregivers eventually gained access to the hospital as well as the

Research Institute by means two small walkways. A special ventilation system

outfitted with individual vertical copper flues drew out the air separately from

each cubicle to the roof to prevent crosscurrents of air. Such an elaborate and

antiquated arrangement sought to protect against airborne germ transmissions. 66 See W.G. Thompson, “The Great Modern Hospital: Present Day Standards of Organization and Equipment,” The Century Illustrated Monthly Magazine (New York) 81 (1910): 87-100.


26

The press found this system quite intriguing and devoted a fair amount of ink to

describe it. The fuss surrounding this veritable “pest house” can be ascribed to

the prevailing germ-consciousness of the American public and persistent fears of

“hospitalism’—meaning nosocomial infections.67

The official inauguration of the hospital took place on October 17, 1910,

and its doors opened to the public the next day. A formal statement announced

that the hospital and all it assets had been placed into a public trust to be

managed by a Board of Trustees that included John D. Rockefeller Jr., Frederick

T. Gates, William Welch, Simon Flexner, and Starr J. Murphy.68 The first Hospital

Superintendent was Nancy Poultney Ellicot, working with her assistant, Mary B.

Thompson. Ellicot had graduated from the Johns Hopkins School of Nursing and

was widely known for her contributions to the welfare of hospital patients.

According to press reports, nearly 2,000 visitors came to attend the open house,

including some of the most prominent physicians, surgeons, and scientists of the

city.69 Simon Flexner and his staff personally escorted some of the local socialites

through the premises, and light refreshments were served in the boardroom.

Notable features of the institution like the special hydrotherapy and electric

treatment room, as well a special diet kitchen received ample praise. During an

early tour of the facilities conducted by George H. Draper, an incoming resident,

67 Jeanne Kisacki, “Restructuring Isolation: Hospital Architecture, Medicine, and Disease Prevention,” Bulletin of the History of Medicine 79 (2005): 1-49. 68 For a valuable overview, consult chapter 4 “The Hospital in its Early Years,” and chapter 10, “The Hospital 1913-1935,” in Corner, A History, pp. 88-107 and 249-283. 69 NY Times, Oct 18, 1910.


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the gleaming modern laboratory apparatus prompted a local academic to remark

“it won’t do you any good if you haven’t any sense.”70 No matter, everybody

seemed to agree: the Hospital was a welcome addition “to make this town (New

York) a great medical center.”71

Physician/investigators: A New Brotherhood?

Healers traditionally experience a perennial tension between compassion

for the sick they treat and intellectual curiosity about the phenomena of the

disease they encounter, its bodily mechanisms and effects. Healers grappling

with human suffering seek explanations and establish causal links as part of

caregiving efforts. By the early twentieth century, however, medicine was in

flux: in the twilight of their profession “old docs “ still fulfilled their traditional

role of counselors, providers of sympathy, comfort, and reassurance. Yet, a new

crop of practitioners “reeking from laboratory” attempted to place their

professional prestige on the fickle shoals of science. Paul H. de Kruif, a former

Rockefeller Institute investigator was deeply skeptical about the shift. “The

practice of medicine is to the greatest extent an art,” he insisted, “ it is partly

craft; it begins to smack of a technology or applied science.”72 The chasm could

not be overcome; “intellectually flabby” doctors should simply apply the results

obtained by true scientists in laboratories. In de Kruif’s view, medical men

70 G. Canby Robinson, Adventures in Medical Education; A Personal Narrative of the Great Advances of American Medicine, Cambridge, Mass.: Harvard University Press, 1957, pp. 90-1. 71 NY Times, Jan 15, 1911. 72 Paul H. de Kruif, Our Medicine Men, New York: The Century Co., 1922, p. 46.


28

lacked the necessary qualities, including “mental rigor” for conducting

laboratory inquiries. Biological investigations required intellectually curious,

impartial, and heartless individuals who would, in the course of their work, be

forced to deny treatments to suffering human controls in the interests of “cold”

science verification.

In fact, Osler had remained essentially a clinician, primarily interested in

manifestations of disease in patients. However, he also believed in the capacity

to distinguish and diagnose disease with the aid of clinical laboratory and

statistics, but expressed personally no deep interest in the study of the essential

biological problems involved that required prolonged laboratory and

experimental investigations. In fact, when it came to therapy, Osler remained a

skeptic, particularly with regards to some of the newer chemical compounds

avidly advertised as panaceas.73

However the novel merger of bench and bedside proposed for the

Rockefeller Hospital demanded a new organizational structure. Under the

supervision of the Board of Directors, management remained in the hands of its

medical director, nominally in charge of admissions and care of the patients as

well as supervising all clinical investigations. The initial Rockefeller Hospital

staff, selected with input from Flexner, consisted of a physician-in-chief—Rufus

Cole—a senior supervisor, George C. Robinson, together with several resident

physicians, the previous mentioned George Draper, Homer F. Swift, Henry Marks,

73 A case study revealing the Oslerian approach is Risse, “The Limits of Medical Science, “ in Mending Bodies, Saving Souls: A History of Hospitals, pp. 399-422.


29

Alphonse R. Dochez, and Francis W. Peabody.74 Part-time specialists included a

surgeon, a radiologist, and soon a non-resident chemist. Originally from Johns

Hopkins, Robinson viewed his assignment as an “adventure into the medical

unknown”75 as well as a welcome step towards a potential academic career. He

was responsible for all referrals and decided on admissions. The residents would

play key roles in both clinical research and patient care under Robinson’s

direction. Each had full control of a ward and was provided with patients—no

more than twenty--to free up time for investigations and thus create the

necessary linkage between the lab and the bedside. Following Cole’s vision, all

prospective hospital physicians were required to possess a solid research

background and expected to organize their own lines of investigation. Prestige,

generous laboratory space, and full-time status took precedence over modest

salaries. Comfortable living arrangements—individual rooms with views and

private baths on the first floor––encouraged celibacy and total dedication.

Science was conceived as a calling linked to an optimal level of

intellectual acuity and asceticism. Akin to a religion, its practitioners were the

priests conducting investigations as a moral imperative. In his autobiography,

Paul de Kruif, a former member of the Research Institute, sarcastically portrayed

that institution as a “temple of science,” a “shrine” attracting the world’s

scientists who came to pay homage. Only select individuals born with the “best

74 Homer F. Swift (1881-1953) carried out studies on syphilis, rheumatic and trench fevers. 75 Robinson, Adventures p. 81.


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brains” were allowed to investigate in its laboratories.76 For the fictional

character in Sinclair Lewis’ Arrowsmith, German bacteriologist Max Gottlieb--

presumably modeled after Simon Flexner--to be a scientist was not a mere

occupation but a pursuit of the truth carried out with unquestioned faith and

dedication. Reputation was their coin, publish or perish their fate. “There must

be knowledge; so many men are kind and neighborly, (but) so few have added to

knowledge,” Gottlieb tells Arrowsmith.77

Indeed, the age of parochialism was over; now scientific rivalry became a

glamorous undertaking. The number of published papers, appearing in new

specialized journals, determined success. Priority and competition made certain

areas of science “hot;” investigators needed to be passionate about their work

and become foils to each other. Determined to hold his ground, Cole countered

that well-trained physician investigators not only had the “sufficient intellectual

equipment” but also used the “most complicated methods of the exact sciences”

to attack the problems of disease. He insisted that no research focusing on

disease would be complete without the observation and investigation of patients

suffering from it.

The success of the Rockefeller Research Institute was attributed citing its

organizational flexibility, interdisciplinary curiosity and recruitment of a cadre of

76 Before his career as a writer, de Kruif worked at the Rockefeller Research Institute from 1920 to 1922. For his candid but biased perspective, see Paul de Kruif, The Sweeping Wind: A Memoir, New York: Harcourt, Brace and World, 1962, pp. 1-55. 77 Sinclair Lewis, Arrowsmith, New York: The Modern Library, 1925, p.367. The author closely collaborated with Paul De Kruif. See Charles Rosenberg, “Martin Arrowsmith: The Scientist as Hero, in No Other Gods: On Science and American Social Thought, Baltimore: Johns Hopkins University Press, 1997, pp. 123-131.


31

young scientists who were allowed to socialize and cooperate with each other.78

Under such circumstances, teamwork was considered essential. Scientists were

prompted to only cooperate with members of their own group but compete “to

the death” against outsiders.79 To achieve such a German inspired “barrack”

mentality, the laboratory directorate needed to set certain intellectual and

methodological standards. From all appearances, Flexner seemed up to the task.

A confident scientist and good administrator, he was strict but fully engaged. As

de Kruif described it in his parody, the “great brain” parceled out “products of

his cerebration to awestruck underlings” who went back to their laboratories

eager and inspired to “prove the validity of the concepts from the master

intelligence.” However, such a scheme had drawbacks; it could stifle individual

creativity and innovation.80

In his initial proposal, Cole had insisted that the Hospital’s senior medical

personnel be prevented from practicing outside the institution. With support

from the Board, they were appointed to salaried, full-time positions, a

controversial and much-debated scheme already supported at the Johns Hopkins

Hospital following the departure of Osler.81 Freed from any unnecessary

distractions to their work, especially the necessity of supplementing their

78 J. Rogers Hollimgsworth, “Institutionalizing Excellence in Biomedical Research: The Case of the Rockefeller University,” in Creating a Tradition of Biomedical Research: Contributions to the History of the Rockefeller University, ed. Darwin H. Stapleton, New York: Rockefeller University Press, 2004, pp. 17-63. 79 Sinclair, Arrowsmith, p. 335. 80 de Kruif, Our Medicine Men, pp.198-201. 81 Berliner, “The Full-Time Plan, in A System of Scientific Medicine, pp. 139-161.


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income through outside consulting fees, the newly minted

physician/investigators could become strangers at the bedside. In fact, Osler had

strongly opposed such an arrangement, fearing that it would create institutional

segregation and foster a depersonalizing climate, isolating hospital physicians

not only from their local counterparts but also compromising relationships with

patients.82

Indeed, the lure of academia and independent professional status

remained legitimate concerns. Clinical investigators were repeatedly urged to

resist monetary temptations and willingly forego the material rewards of private

practice. This was still the era of great and prosperous practitioners, mostly

members of the select Association of American Physicians. Although affiliated

with large hospitals, these “lords of the clinic,” eluded the restraints of

academia and eyed with skepticism the claims of scientific medicine. For their

part, investigators continued to express disdain for practitioners in the trenches.

Manners still trumped the hard truths of human pathology. Trying to get away

with “art” was quaint, but battling disease without a real clue of the phenomena

occurring in the bodies of their sick charges increasingly unacceptable. Instead of

bemoaning the loss of bedside art, doctors should be “born again to the

microscope.”

In Arrowsmith, Gottlieb/Flexner warned of the dangers lurking in the

realm of translational research: eager practitioners rushed around claiming to

82 In fact, Osler did not mince words, calling full-time physicians “a set of clinical prigs, the boundary of whose horizon would be the laboratory and whose only human interest would be research.” “Sir William Osler: On Full-Time Clinical Teaching in Medical Schools,” Canadian Medical Association Journal 87 (Oct 6, 1962): 763. The essay was originally written at Oxford, September 1, 1911, addressed to Ira Remsen, President of Johns Hopkins University.


33

heal people. In their eagerness to please patients, doctors wished to snatch bits

of science and questionable reports of cures, then draw attention and publicity

while prematurely trying new drugs and vaccines before the research was

completed, thus “spoiling all clues” before proper testing.83 Increasingly,

scientific prestige often had another important impact, prompting certain

clinicians to leave the bedside altogether and exclusively pursue careers in

biomedical research.

Under Cole’s leadership, a similar environment was created at the

Rockefeller Hospital, this one loosely organized around laboratories and wards.

In sharp contrast to academic medical centers arranged according to rigid

scientific disciplines and clinical specialties, the Hospital focused their research

on contemporary health problems. Like its neighbor, this novel arrangement

allowed for new directions and strategies, especially evident in subsequent

research conducted by several hospital staff members, including Oswald Avery.84

Cole reiterated that the physician’s closeness to the bedside would keep his

mind on the real purpose of the investigation instead of wandering ever more

deeply into basic research.

Resident physicians discussed their patients and ongoing research projects

over breakfast, lunch, and dinner. After the Hospital opened in 1910, the

medical staff organized a biweekly Journal Club, a forum for discussing articles

with broad appeal published in the current medical literature. In time, Alfred E.

83 Sinclair, Arrowsmith, p. 290. 84 Oswald T. Avery (1877-1955) joined the Research Institute in 1913. He was interested in bacteriology and immunochemistry.


34

Cohn became its leader and chief proponent. Afternoon teas in the hospital’s

library further cemented this stimulating and intellectually nourishing

environment for the clinical investigators. Cole was credited for his tireless

efforts to establish professional parity among Institute and Hospital staffs

through carefully orchestrated social contacts. His objective was to allow his

young clinicians to mingle with Institute researchers. 85 The goal was to not only

establish a climate of camaraderie and common aspirations but also create

conditions for scientific cross-fertilization. On occasion, medical residents would

join their colleagues down the street for lunch and participate, according to De

Kruif, in “scintillating” talk with some of the most prominent bio-scientists in the

world, including Jacques Loeb and Nobel Prize winner Alexis Carrel, the latter

widely known for his work on cancer.86

Research Institute members such as Flexner, Peyton Rous, Hideyo

Noguchi, and others reciprocated, visiting the Hospital.87 Among them was

Samuel J. Meltzer, a European immigrant physician and scientist who headed the

Institute’s Department of Physiology and Pharmacology since 1904. Meltzer was

particularly interested in the actions of adrenaline as well as methods of

85 James H. Means, The Association of American Physicians, New York: Blakiston Division, McGraw Hill, 1961, p. 210. 86 Carrel (1873-1944), the French physician and surgeon. was awarded the Nobel Prize in 1912. He worked at the Rockefeller Institute from 1906 to 1939. See “How the Doctors are Waging War on Cancer: Dr. Alexis Carrel’s Experiments at the Rockefeller Institute and Other Developments of an International Crusade,” NY Times, Jan 8, 1911. 87 For information about Hideyo Noguchi () see Atsushi Kita, Dr. Noguchi’s Journey: A Life of Medical Search and Discovery, Tokyo, Kodan Sha, 2003.


35

artificial respiration.88 Eventually, a covered corridor, heated during winters,

came to connect both Institute and Hospital buildings, facilitating collegial

exchanges. Like Cole, Flexner at the Institute was quoted as stressing the greater

importance of harmony, serenity and brotherhood among his investigators over

their scientific output and capacity to save lives.89

Given the growing importance of biochemistry, Donald D. Van Slyke,

another scientist already working in the Institute, was transferred in 1914 to the

Hospital with his associate, Glenn Cullen. He later admitted to an initial “deadly

doubt” about the relevance of his work for medicine, but he was soon able to

focus on the a variety of metabolic problems related to oxygen and carbon

dioxide in the blood as well as diabetic acidosis. Nevertheless, Van Slyke’s

comment exposed the perennial problem of fusing results derived from basic

investigations with clinical phenomena. De Kruif describes a luncheon during

which even Loeb somewhat sarcastically uttered that medical science was a

contradiction on terms.90 At the time, MDs were still viewed as “applied”

scientists when contrasted with PhD investigators who were creatively involved

with “basic” questions. Unfortunately the latter could not write orders and issue

prescriptions at the Hospital since they lacked a medical license, a frequent

source of frustrations and frictions.

From occasional glimpses, professional life at the Rockefeller Hospital

88 A. Mcgehee Harvey, “ Samuel J. Meltzer: Pioneer Catalyst in the Evolution of Clinical Science in America, Perspectives in Biology and Medicine 21 (1978): 431-440. 89 De Kruif, The Sweeping Wind, p. 55. 90 The German-born Loeb (1859-1924) became famous for his biochemical studies.


36

appeared to flourish in an environment of friendship and mutual trust. This

milieu encouraged close mentoring relationships essential for perpetuating the

presumed virtue of scientific research as well as maintaining ethical standards of

conduct. So far, however, little is known about their inner lives. Busy and

focused on their research and patients, these men seemed to lack the time for

personal reflection and writing about their conflicting responsibilities as

investigators and clinicians, and the inevitable stress and uncertainty

surrounding these dual tasks. Only decades later, in their memoirs, a few waxed

nostalgic recalling the early days of the institution. Arthur W.M. Ellis praised

“the companionship and friendship of the group” assembled by Cole. He

considered himself very lucky to have been chosen. “They were good days in

every way,” he recalled. Robinson was impressed about the gleaming, well

equipped laboratories and the very interesting patients he was privileged to

see.”91 He recalled his two-year stint at the institution as “truly a privilege.”

Indeed, “life in the Hospital was full of joy.” The environment was ideal: the

East River with its great span of light and night, and its lapping waters; a blazing

hearth about which we gathered after dinner—all these things gave a setting in

which friendship deepened and true sympathy thrived.” 92

Robinson was not only impressed by the prevailing atmosphere and

commitment to clinical investigation, but valued the friendly companionship and

“delightful social relations.” According to de Kruif, Flexner at the Research

91 Robinson, Adventures, pp. 99-100. 92 Ibid. p.95.


37

Institute eschewed all romantic contacts among staff members as “improper;”

they were considered potentially damaging to institutional morale and

reputation. During the hot New York summers, the researchers played baseball

games together on an empty lot in front of the buildings overlooking the East

River. The Hospital also featured tennis courts and landscaped gardens

surrounding the building. In Robinson’s opinion, “mutual regard for each other’s

work and cooperation whenever possible, fostered a happy situation.”93 Still,

beyond outside dinners, occasional attendance at concerts and clubs, and

summer vacations, life was quite regimented and monotonous. Extramural

networking, for its part, was fostered through the establishment of the American

Society for Clinical Investigation in 1907 under the leadership of Samuel Meltzer.

The so-called “Young Turks” held their yearly meetings in Atlantic City.94 A new

influential brotherhood of hybrid physician-investigators began to spread across

America.

The Birth of Volunteer Research Subjects

The presence of patients was essential for the success of this new scientific

enterprise at the Rockefeller Hospital.95 In his memoirs, Robinson, the first chief

resident, bragged about his ease in “assembling the clinical material.” We still

93 Robinson, Adventures, p. 99. 94 J.H. Austin, “A Brief Sketch of the History of The American Society for Clinical Investigation, Journal of Clinical Investigation 28 (1949): 401-8. 95 Edward H. Ahrends, “The Birth of Patient-Oriented Research as a Science, (1911)” Perspectives in Biology and Medicine 38 (1995): 548-543.


38

know very little about the individuals who were admitted to the institution. So

far their voices appear to have been lost in time, replaced by technical

descriptions of their pathology, laboratory tests, and the eventual outcome of

their illness. According to one historian, admissions at the Rockefeller Hospital

included the rich and poor, artisans and housewives, physicians and clergymen,

even high officials like the governor of the state and the mayor of New York.96

Not surprisingly, therefore, the hospital authorities mounted a concerted

institutional effort to safeguard their identity and privacy. Most published case

reports feature only case record numbers, age, diagnosis, and outcome. 97

Following the example of Johns Hopkins Hospital, the Rockefeller institution

featured a number of single private rooms. In fact, as previously noted, ten of

them were located on the third floor, together with two semiprivate ones. Good

nursing care was to be provided by a cadre of highly trained Hopkins graduates.

Empathetic nurses were indispensable in helping individual patients adjust to

hospital life and maintain ward discipline. “Although investigation has been

stressed,” Cole announced, “it has been the purpose of the hospital to provide

the best available nursing care and the use of every procedure known to benefit

and relieve disease.”98

96 Corner, A History, pp. 280-282. 97 Patient records from the Rockefeller Hospital have been collected and preserved on microfilm in its archives apparently without any identifiable data concerning names, addresses and occupations. Requests from the author to access this material in 2005 were denied under the terms of the HIPAA legislation for the protection of patients’ medical information. 98 Rufus Cole, “The Hospital of the Rockefeller Institute, New York,” in Forschungsinstitute, vol.2, p. 492.


39

Prospective patients were either self-referred or recommended by other

physicians from the NYC area. One must presume that they or often their parents

tacitly supported the ideals and potential payoffs of scientific medicine and were

thus eager to cooperate. Contrary to popular apprehensions, Cole believed that

the arriving patients fancied that the Rockefeller Hospital staff possessed an

“increased power to help.”99 Indeed, from the start, the institution sought to

attract its clientele by announcing that it would “devote all their time and

energy to the cure of those entrusted to their care.” The Hospital emphasized

the “paramount right” of every patient to receive the most effective treatment

available to the attending physicians.

Even more important was the fact that under the approved institutional

bylaws, no charges could be imposed on patients treated at the Hospital, not

only for room and board, but also for all professional services and tests, a

significant departure from the Hopkins model where the private rooms were

reserved for paying patients. Although this feature was widely known, the

Rockefeller Hospital issued another official announcement in January 1916,

selectively inviting persons currently ill from acute pneumonia, heart disease,

diabetes, and nephritis to seek free care.100

Another unusual feature at the Rockefeller Hospital was the length of the

patient’s stay, usually driven by clinical events, professional judgment,

institutional constrains, and medical economics. Since they were primarily 99 Rufus Cole, “The Modern Hospital and Medical Progress,” Science 64 (Aug 6, 1926): 128. Cole’s address was delivered at the New Haven Hospital during celebrations of its 100th anniversary. 100 NY Times, Jan 6, 1916.


40

considered research subjects and their hospitalization entirely covered by

Rockefeller endowments, patients sometimes remained at the Hospital for weeks

and even months while it’s investigating clinicians continued their observations

and testing.101 Once submerged in the new institutional world they had helped

create it was often difficult to depart. In a letter to Flexner in 1911, Gates

reproduced a testimonial from one of the early patients who expressed great

satisfaction about her care as well as reluctance to leave the institution. Five

years later, Gates tried to lure his master, John D, Rockefeller Sr., to the

Hospital for a checkup, writing to him “the physicians are extremely polite,

gentle and courteous, and the nurses are very paragons of their tribe.” However,

the old man—a believer in homeopathic medicine—demurred. He only once set

foot on the institution at the urging of his son, but never got beyond the lobby

and promptly retreated to his carriage.102

Whereas in earlier times the key attributes of patienthood had been courage

and endurance, the new situation also demanded a generous dose of stoicism.

Frequent laboratory testing including blood withdrawals for counts and

bacteriological cultures as well as spinal taps and injections were essential

functions to gather data for the ongoing research projects. Except perhaps for

infants and children brought in during true emergencies, people with higher

educational and social standing would have been potentially more inclined to put

101 Case 6, 20 year=old Jennie remained for 80 days; she was then transferred to the New York Orthopedic Hospital for further treatment. See F.W. Peabody, G. Draper, A.R. Dochez, A Clinical Study of Acute Poliomyelitis, New York: Rockefeller Inst. Med Research, 1912. 102 Much has been written about the Gates and Rockefeller motivations, their efforts to reverse the tycoon’s public image of a greedy, heartless and union-busting tycoon.


41

up with such often painful examinations and become partners in the investigative

enterprise. To compensate for the ordeal, close and frequent observations

carried out with the aid of sophisticated medical equipment offered hope for a

better diagnosis and therapy.103 In one instance, the press chose to extol the

virtues of the hospital’s diagnostic electrocardiography; in a completely wired

hospital environment, heartbeats could be recorded “a mile away” providing an

intimate look at the inner workings of this vital organ.104

Barely nine months after opening its doors, a newspaper article described

how the wealthy eagerly competed with the poor to enter the Rockefeller

Hospital. Concerned parents of children experiencing paralytic symptoms sought

admission to the emergency room and isolation building for study and treatment.

The effort was deemed worthwhile: “the fortunate few whose application is

accepted will know that under Director Flexner the children will have medical

services, room, nursing and scientific facilities such as are afforded for love or

money nowhere else in the world.”105

Other factors bringing patients to the Rockefeller Hospital may have been its

clinical originality and lavish furnishings, elements responsible for acquiring a

unique personality and mystique that persists into our own days. In spite of

official declarations of simplicity and economy, reporters commented on the

“luxurious manner” in which every hospital department was outfitted. This

103 Science 32 (Oct 28, 1910): 587-588. 104 NY Times, Jan 1, 1911. 105 NY Times, Jul 9, 1911.


42

home-like atmosphere and the “air of comfort and cleanliness” pervading the

institution would make it difficult for some patients to leave. ”No such facilities

have hitherto been at the disposal even of the wealthiest of patients,” wrote a

New York Times reporter.106 What is truly remarkable is that at a time when

only 10% of the sick sought care in hospitals, there were already 70 applications

for admission to the Rockefeller Hospital before opening day. For the next four

months the list apparently ballooned to 2,000, although the average yearly

admission rate apparently did not exceed 200 patients.107

A few tables and case reports imbedded in scientific publications provide

fragmentary information on Rockefeller Hospital patients. In 1912, Alphonse

Dochez listed 37 patients afflicted with lobar pneumonia, probably among the

earliest admissions. No gender and occupation were listed, although a majority

was supposed to have been males. Their average age was thirty with only four

over the age of fifty. The institutional mortality was 46%, comprising a somewhat

older cohort--40 years—all suffering from severe infections that ended their lives

on average within the first four days of hospitalization. The exception was a 54

year-old patient who contracted a post-pneumonic nephritis and died after a 42-

day stay.108

A closer look at the 34 published polio cases admitted to the Rockefeller

Hospital during the summer and fall of 1911 reveals a profusion of infants and

106 NY Times, Oct. 18, 1910. 107 These statistics appear in the Board’s minutes; quoted in Corner, A History, p. 97. 108 A.R. Dochez, “The Occurrence and Virulence of Pneumococci in the Circulating Blood During Lobar Pneumonia and the Susceptibility of Pneumococcus Strains to Univalent Anti Pneumococcal Serum,” J. Exper. Med. 16 (Nov 1, 1912): 680-692.


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young children. Twenty were males, fourteen females, ranging from a 20 year-

old woman to a 3 month-old baby girl, nearly a third under the age of two. The

patients’ average age was close to four and the inmates remained in the

institution for an average of five weeks. Most exhibited obvious and progressive

paralytic symptoms; 67% were eventually discharged “improved,” still suffering

from their crippling disabilities, while 26% died from respiratory failures, usually

a few days following admission. A newspaper report in July 1912 mentions that

91 “virulent” polio cases were brought to the Rockefeller Hospital from an

epidemic outbreak on New York’s East Side.109 A study on the diagnostic

importance of cerebrospinal fluid lists a total of at least 126 cases tested in the

first two years of hospital operations, although most would have been initially

seen at the Dispensary and admitted to the adjacent isolation pavilion.110

Unlike the reluctant philanthropist, eagerness to become a patient at the

Rockefeller Hospital remains somewhat puzzling if one considers the

contemporary climate of public suspicion surrounding medical research.

Traditionally mostly the powerless, including the poor, prisoners, aged, and

physically disabled individuals—frequently dubbed “human guinea pigs”—were

subjected to such testing. Already tainted by his business deals, Rockefeller’s

philanthropic endeavors had come under intense scrutiny and criticism as

109 NY Times, Jul 21, 1912. 110 Francis R. Fraser, “A Study of Cerebrospinal Fluid in Acute Poliomyelitis,” J. Clinical Investigation 18 (Sep 1, 1913): 242-351.


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potentially detrimental to human welfare.111 Yet, it appears that incoming

patients were not specifically asked for permission to be subjected to tests. More

likely, the request for admission implied a willingness to work with the

physician/investigators since their studies could presumably help improve, even

save their lives.

By the time the Rockefeller Hospital opened its doors in 1910, allegations of

“human vivisection” swirled around NYC, spelled out in pamphlets and

newspaper articles.112 Flexner tried to deflect anxieties stirred up by the

prospects of human experimentation and was quoted in the New York Times as

saying that “once we have tried our remedies with satisfactory results upon

animals, there is little risk to human beings, and of course in treating the latter

we shall proceed with the utmost caution.”113 For his part, Cole recalled in 1926

that patients seemed not afraid of being experimented upon. Obviously he was

referring to adults. Children subjected to the fear and pain of multiple spinal

taps and bleedings probably would have disagreed.

The hospital experiences of two siblings typified the fears and frustrations of

a New York family with five children living in a crowded flat on Lexington Ave in

Manhattan “with flies, mosquitoes, bedbugs and roaches” facing the specter of

111 For an overview, Howard Berliner, A System of Scientific Medicine: Philanthropic Foundations in the Flexner Era, New York: Tavistock, 1985. 112 See R.M. Pearce, “The Charge of Human Vivisection As Presented in Antivivisection Literature,” Journal of the American Medical Association 62 (1914): 659-668. For details, see Bernard Unti, “The Doctors Are So Sure That They Only Are Right’: The Rockefeller Institute and the Defeat of Vivisection Reform in New York, 1908-1914,” in Stapleton, Creating a Tradition, pp. 175-190. 113 NY Times, May 31, 1908. See also Simon Flexner, “Medical Research and Its Organization, “ Science 66 (Jul1927): 71.


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polio in the fall of 1911. Their oldest daughter, Hannah T., a strong and healthy

4 year-old, was admitted to Ward 1 on October 3rd after her legs became weak

and she was unable to walk. The next day, her younger, well nourished 2 year-

old brother Patrick T. followed, dragging one of his legs. Both received a

diagnosis of acute poliomyelitis and were subjected to numerous laboratory

tests, including repeated sampling of spinal fluid and blood that made them, in

the official case report, “moody.” In fact, Hannah routinely complained of pain

when touched by physicians and nurses. Patrick showed no evidence of paralysis

and according to the hospital record, it was “hard to distinguish pain from

temper,” a fact that prompted his discharge a week later. Both received

symptomatic treatment: painkillers and cathartics. Although Hannah displayed

some right thigh paralysis, her mother grew impatient, and on October 20th

insisted in taking her home. To the surprise of her caregivers, the child got

dressed without complaining of pain and promptly left the hospital.114

In other establishments, incoming patients subjected to long stays usually

sought support and encouragement from those already hospitalized, joining their

new institutional “family”, a cohesive group prevalent in small wards. Still

missing for the Rockefeller Hospital are signs of institutional socialization and

formation of a ward community. Moreover, in the case of sick infants and

children, would anxious parents be allowed to stay? Given all the investigative

activities taking place in adjacent laboratories, what kind of visiting

arrangements shaped hospital life? Whether some inmates became “stars” or

114 See cases 4 and 32, in F.W. Peabody, G. Draper, A.R. Dochez, A Clinical Study of Acute Poliomyelitis, New York: Rockefeller Inst. Med Research, 1912.


46

“newsworthy”—features in professional journals, newspapers and popular

magazines, still needs further elucidation.

Diseases: Targets for Research

Flexner’s early intention in 1902, shared with Welch, was to establish a

modern and fully equipped hospital to “provide only for selected cases of

disease.”115 By the time the Rockefeller Hospital opened its doors eight years

later, clinical investigation was touted as solving contemporary health problems.

Spooked by sensitivities of human vivisection, a defensive Board of Directors

issued a press release: ”By filling the hospital with only three of four kinds of

disease, it wll be possible for the staff to concentrate upon these for the purpose

of study.”116 The final choice included pneumonia, mostly its lobar appearance,

followed by poliomyelitis, syphilis, heart disease--eventually extended to

rheumatic fever, diabetes, nephritis and encephalitis--and intestinal conditions

of metabolic significance.

Such priorities indeed reflected “some of the most pressing problems of

the day,”117 Dominating the group were infectious diseases easily contracted in

crowded circumstances and common in a large metropolis such as New York City.

In time, many hospital studies would attempt to identify the presumptive

etiological microorganisms--bacteria and viruses—and determine the chemical,

115 Flexner to Welch, April 8, 1902, in Minutes of the Board of Directors, quote in Corner, A History, p. 89. 116 NY Sun, Oct 18, 1910. 117 Journal of the American Medical Association 190 (Oct 22, 1910): 1482.


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pathological, and immunological responses shaping the clinical events.

Additionally, the attending physician/investigators in these early years tried to

evaluate promising prophylactic and therapeutic agents, including the use of

morphine, digitalis, and oxygen.

Pneumonia

Cole’s own research focused on acute lobar pneumonia, a very common

winter occurrence in New York City, notably afflicting young and robust males.

Mortality was estimated at over 20% and conventional treatment remained

symptomatic, ranging from bloodletting to opiates, oxygen to calomel, emetics

as well as alcohol. Working closely with two other resident physicians, Dochez

and Marks, Cole attempted to replicate the previous successes in diphtheria with

the development of an anti-pneumococcus serum. Yet, he faced difficulties since

it was discovered that there were four distinct strains of offending bacteria,

each displaying specific antigenic characteristics and virulence.118 In an early

study, the sera obtained from 14 pneumonia patients during various stages of

their disease were found to contain protective substances after the ninth day.

This was a critical turning point or “crisis” after which the disease would move

toward death, or enter a period of spontaneous resolution and recovery. 119

118 Rufus Cole, Pneumococcus Infection and Immunity, New York, Elliott Publ., 1915; reprinted in the New York Medical Journal (Jan 2 and Jan 9, 1915). See also Ernest Stillman, “A Contribution to the Epidemiology of Pneumonia,” J. Exper. Med. 24 (Dec 1, 1916): 651-670. 119 A.R. Dochez, “The Presence of Protective Substances in Human Serum During Lobar Pneumonia,” J. Exper. Med. 16 (Nov 1. 1912): 665-679. For details, see Scott H. Podolsky, “The Advent of Type-Specific Antipneumococcal Serotherapy,” in Pneumonia Before Antibiotics: Therapeutic Evolution and Evaluation in Twentieth-Century America, Baltimore: Johns Hopkins University Press, 2006, pp. 13-21.


48

Francis W. Peabody approached this disease from a functional angle, studying

the oxygen and carbon dioxide levels in the blood of twenty-five cases of

uncomplicated pneumonia that experienced a mortality of 42%.120

On April 1913, the press announced that inoculations of specific serum for

the most prevalent pneumococcus strain had been judged to be useful.121

Obtained from the blood of inoculated horses, it seemed to offer a measure of

protection although. Ultimately, with the assistance of Avery since 1913, the

administration of specific sera for type I appeared to lower mortality rates for

the disease, although many patients recovered spontaneously.122 Another early

resident, Francis W. Peabody, studied the effects of pneumonia on respiration

and blood chemistry. In another demonstration of close collaboration, Alfred

Cohn investigated the actions of morphine and digitalis in pneumonia since the

disease caused frequent and severe cardiac strain. His 1917 article reflected the

growing medical armamentarium available to mitigate the symptoms of the

disease and create better outcomes.123 Oxygen therapy inspired by Peabody’s

research eventually led to the installation of chambers for its controlled

120 F.W. Peabody, “The Carbon Dioxide Content of the Blood in Pneumonia,” J. Exp Med. 16 (Nov 1, 1912): 701-718. See also his article “The Oxygen Content of the Blood in Lobar Pneumonia,” J. Exper. Med. 18 (Jul 1, 1913): 7-17. 121 NY Times, Apr 1913. 122 Oswald T. Avery, Henry T. Chikening, Rufus Cole and Alphonse R. Dochez, Acute Lobar Pneumonia: Prevention and Serum Treatment, New York: Monograph No 7, Rockefeller Inst. Med Research, 1917, pp. 76-101. 123 A.E. Kohn and R.A. Jamieson, “The Action of Digitalis in Pneumonia,” J. Exper. Med. 25 (Jan 1, 1917): 65-82.


49

administration in other severe respiratory conditions.124 All such studies proved

useful for US Army and Navy physicians managing pneumonia outbreaks in the

barracks before and during WWI saving lives, but diagnostic difficulties and

conflicting claims of its efficacy created skepticism. More important, perhaps,

were the new insights obtained into the biology of infectious agents and how

they affected the human immune system, a subject subsequently developed by

Avery.125

Poliomyelitis

In the summer of 1911, the Hospital’s research program shifted into high

gear during a severe outbreak of polio in the city.126 Caused by an invisible virus,

the disease was viewed as a generalized infection eventually coming to “rest” in

the spine and brain of its sufferers. Polio’s epidemiological pattern baffled

experts: instead of striking the worst city slums, children from higher income

suburban and rural areas became sick. According to Flexner, vigorous health

failed to offer protection. Transmission was assumed to occur through nose and

throat secretions. The initial challenge for clinicians was diagnostic: faced with

crying infants, a plethora of vague complaints uttered by frightened small

children or sketchy stories of distress from concerned parents, how could they

determine the presence of polio, especially before the onset of telltale

124 W.C. Stadie, “The Oxygen of the Arterial and Venous Blood in Pneumonia and its Relation to Cyanosis,” J. Exper. Med. 30 (1919): 215. 125 For details, Rene Dubos, The Professor, the Institute and DNA, New York: Rockefeller University Press, 1976. 126 David M. Oshinsky, Polio; An American Story, New York, Oxford University Press, 2005, pp. 8-23.


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paralyses?127 To assist bewildered clinicians, periodic microscopic and chemical

examinations of spinal fluid and blood sought to gage the presence and intensity

of nervous system involvement.

Back at the Rockefeller Hospital, Peabody, Dochez, and Draper with their

24-hour rotating staff struggled to understand the clinical nuances of this

mysterious, contagious disease that often started as an innocuous flu-like

ailment before the onset of devastating paralyses or deadly suffocations. To be

sure, these investigators took pains to assess the successive stages and

manifestations of this disease in their quest to sharpen their diagnostic and

prognostic skills while administering painkillers and cathartics. The results were

compiled and published to help average practitioners distinguish the disease

from other respiratory and gastrointestinal ailments. For their part, public health

officials employed such clinical cues to press for notification and isolation of

suspected cases, part of their preventive efforts to contain this scourge.

At the Institute, meanwhile, Simon Flexner and Paul F. Clark were already

busy studying polio, caused by a filterable agent or “virus” discovered by the

Austrian scientist Karl Landsteiner in 1908.128 Like in meningitis, Flexner insisted

that polio was solely transmitted through nasal and throat secretions, then

invading directly the brain and spinal cord, a theory widely adopted by his

127 Naomi Rogers, “Garden of Germs: Polio in the United States, 1900-1920,” in Dirt and Disease: Polio Before FDR, New Brunswick, NJ: Rutgers University Press, 1992, pp. 9-29. 128 S. Benison, “Poliomyelitis and the Rockefeller Institute: Social Effects and Institutional Response,” J. History of Medicine 29 (1974): 74-92.


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clinical colleagues and health officials in the greater New York Area.129 He thus

tried to replicate his successful investigations concerning cerebrospinal

meningitis: find a susceptible animal model, conduct intraspinal inoculations

with material containing the virus, then culture and transmit the agent to other

animals. Using imported rhesus monkeys, the only animal susceptible to the polio

agent, experimentation at the Rockefeller Institute was expensive, hazardous—

the beasts bit their handlers—and complex. Flexner presumed that surviving

animals inoculated with the virus would possess potential antiviral antibodies in

their blood and spinal fluid; a similar event could be presumed in recovering

humans.130 This specific “anti poliomyelitis” serum--mostly derived from human

blood--was then administrated to hospital patients in the New York City area,

with uncertain results.131 Not well known was the fact that during the polio

crises Flexner refused his clinical colleagues access to his experimental

laboratory where he was pursuing his own research with the virus.132

Syphilis

At this time, venereal diseases were ubiquitous in urban areas like New

129 S. Flexner, “ The Nature and Manner of Conveyance and Means of Prevention of Infantile Paralysis, Science 44 (1916): 73-61. 130 S. Flexner and P.A. Lewis, “Experimental Epidemic of Poliomyelitis in Monkeys,” J. Exper. Med. 12 (1910): 227-255. 131 H.L. Amoss and A.M. Chesney, “A Report on the Serum treatment of Twenty Six Cases of Epidemic Poliomyelitis,” J. Exper. Med. 25 (Apr 1, 1917): 581-608. For details, Rogers, Dirt and Disease, pp. 72-105. 132 See McGehee Harvey, Science at the Bedside, p.97.


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York, afflicting all social classes.133 Both Flexner and Noguchi went on to confirm

the etiological role of the treponema pallidum in syphilis, although potential

vaccines and sera failed to become useful in treating the disease. While

traditional therapeutic specificity had been in retreat for more than a century,

new results obtained from selected chemical studies acquired an ever-greater

importance. In fact, with financial support from the Rockefeller Institute, a new

arsenical compound, discovered by the German scientist Paul Ehrlich’s named

Salvarsan, promised an alternative option—a “magic bullet”—not only to relieve

symptoms but cure disease.134 Recurrence and cases of hypersensitivity to

Salvarsan in Germany brought complaints and accusations of charlatanism. In

1914, Ehrlich was drawn into a nasty legal battle as a defense witness for the

Frankfurt Hospital. The institution was being sued by a local newspaper for

allegedly forcing hospitalized prostitutes suffering from syphilis to submit to

treatment with the compound.135

At the behest of Ehrlich, another Rockefeller Hospital resident, Homer

Swift, studied syphilis and monitored the administration of the drug. In spite of

its instant popularity, routes of injection and optimal dosage remained

uncertain. Swift was particularly interested in the neurological complications of

133 For details, Allan M. Brandt, No Magic Bullet: A Social History of Venereal Disease in the United States Since 1880, New York: Oxford Univ. Press, 1987. 134John Parascandola, “The Theoretical Basis for Paul Ehrlich’s Chemotherapy, Journal of the History of Medicine 36 (1981): 19-43. See also J. Mann, The Search for the Perfect Drug, New York: Oxford University Press, 1999, especially pp. 1-209. 135 Patricia S. Ward, “The American Reception of Salvarsan,” Journal of the History of Medicine 36 (1981): 44-62. For a biography of Nobel Prize winner Ehrlich, Ernst Båumler, Paul Ehrlich: Scientist for Life, New York: Holmes & Meiser, 1984.


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tertiary syphilis, and with the assistance of Arthur W. Ellis they both developed

an intra spinal delivery method for a mixture of blood and Salvarsan that proved

of value in the treatment of tabes dorsalis.136 Despite great efforts, however,

Swift was unable to reproduce the disease in experimental animals.

In the meantime his Research Institute colleague, Hideyo Noguchi,137

worked with luetin 138an extract of the agent believed to be responsible for

syphilis, hoping that it would become a potential diagnostic marker to screen

and identify the disease. Unfortunately, his skin tests with luetin on 146 children

ages 2-18 drew the ire of contemporary members from the Vivisection

Investigations League who accused Noguchi of spreading a “blood disease” and

threatened a lawsuit and prison.139 In a letter to the editor of the New York

Times in 1913, Flexner categorically defended the inoculations, urging the public

not to be misled or needlessly alarmed: the Rockefeller Institute never

conducted dangerous experiments on patients.140

Cardiovascular Disease

Another Rockefeller Hospital research target was the heart and

136 A.W.M. Ellis and H.F. Swift, “The Direct Treatment of Syphilitic Diseases of the Central Nervous System,” New York Med. Journal 96 (1912): 53. 137 The Japanese investigator Hideyo Noguchi (1876-1928) worked at the Institute between 1904-1928. In addition to his studies about tertiary manifestations of syphilis, he was also interested in yellow fever. 138 For more discussions, see Sydney A. Halpern, Lesser Harms: The Morality of Risk in Medical Research, Chicago: University of Chicago Press, 2004. 139 NY Times, May 21, 1912. For details, see Susan E. Lederer, “Hideyo Noguchi’s Luetin Experiment and the Antivivisectionists,“ Isis 76 (Mar 1985): 31-48. 140 NY Times, Dec 12, 1913.


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cardiovascular circulation, developed by Canby Robinson and George Draper.

Their early interests focused on functional measurements of cardiac output and

failure in several clinical conditions. The prevalence of such ailments reflected

New York’s more stressful and less active lifestyle as well as the prevalence of

rheumatic fever and its most dangerous complication: endocarditis. Alfred E.

Cohn, a former pupil of the English pioneer of electrocardiography, Sir Thomas

Lewis, soon joined in this endeavor.141 In March 1911, the Hospital acquired its

own electrograph machine, the third available in the city. Soon, in their quest to

achieve greater diagnostic precision, Cohn and Robinson began to administer and

interpret electrocardiographs in an effort to first assess its size and role of the

heart in blood flow, as well as cardiac arrhythmias, coronary occlusion and other

abnormalities. With the electrodes in place and without disturbing their patient--

some of them small children--the investigators extended their wires across

corridors to connect to the big machine, taking up an entire room.142 Cohn

worked with Swift on the relationship between streptococci and rheumatic fever,

and the effects of the latter on cardiac structure and function. Heart valve

damage from endocarditis created by complications of rheumatic fever was also

clinically studied together with the action of drugs on this organ that included

141 Alfred E. Cohn (1879-1957) was one of the first full-fledged cardiologists in America. He retired in 1944. 142 G. Canby Robinson, “A Study with Electrocardiograph of the Mode of Death of the Human Heart,” Journal of Clinical Investigation 16 (Sep 1, 1912): 291-302. The conclusion, derived from four deaths due to pneumonia established that the heart was not the last organ to die.


55

atropine, digitalis and quinidine.143 In related research, Alexis Carrel’s

experimental procedures, notably blood vessel repair and organ transplantation,

offered new vistas and hope for patients suffering from cardiovascular

ailments.144

Intestinal and metabolicl conditions

By 1913, Frederick M. Allen continued Herter’s early metabolic studies

with a focus on diet and metabolism. Allen had been studying diabetes at

Harvard and attempting to produce the disease in animals. A presumed cure was

announced by the Rockefeller Institute in October 1915: in addition to “starving

out the disease” with a low carbohydrate diet, injections of sodium bicarbonate

and chloride prevented acidosis, a decades-old approach of questionable

efficacy.145 By early 1916, however, Allen unveiled his new program: thirty

patients were being subjected to long initial periods of fasting combined with

vigorous physical exercise. Indeed, inpatients ran up and down the hospital’s

eight flights of stairs twenty times a day; others walked ten miles around the

grounds in the open air, skipped rope, or played with medicine balls. “We are

making athletes out of them,” Allen’s colleague Edgar Stillman told reporters.

For their troubles, the lean and famished patients were given whisky “for the

143 A.E. Kohn, “The Influence of Digitalis on the T Wave of the Human Electrocardiogram,” J. Experimental Med. 21 (Jun 1, 1915): 593-603. 144 Shelley McKellar, “Innovation in Modern Surgery: Alexis Carrel and Blood Vessel Repair,” in Stapleton, Creating a Tradition, pp. 135-150. 145 NY Times, Oct 10 and 11, 1915.


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sake of good tone.”146

The Tribulations and Ethics of Clinical Research

In retrospect, research at the Rockefeller Hospital would now be termed

“small science”, conducted in an institution with an extremely limited number of

patients, few laboratories, and just a handful of scientists and residents. From

our vantage point, it certainly seemed to possess all the qualities of a boutique

institution, not the usual monumental medical complex and assembly line.

However, the setting allowed, in Rufus Cole’s words, “for painstaking studies of

closely related phenomena in the same patient.”147 According to one of the

resident physicians, Alfred E. Cohn, boundaries between fundamental and

clinical investigation needed to remain flexible and vague to facilitate the

proper transfer of knowledge.148 One prime example was Oswald Avery’s

scientific career, and the steps that led from studies about the etiology of

pneumonia to molecular biology and eventual identification of DNA.149

Topics for investigation at the Hospital were chosen in consultation with

Flexner and the Board of Directors. Led by Cole, the work was conducted in well-

equipped and staffed laboratories located on the 7th floor comparable to those in

146 NY Times, Feb 13, 1916. See also F.M.Allen, E. Stillman and R. Fitz, Total Dietary Regulation in the Treatment of Diabetes, New York: Monographs of the Rockefeller Institute, Oct 1919. 147 Cole, The Hospital, Forschungsinstitute, p. 492. 148 See Alfred. E. Cohn’s introduction to a new journal, “Purposes in Medical Research,” Journal of Clinical Investigation 1 (Oct 1924): 111. 149 See Olga Amsterdamska, “Between Pneumonia and DNA: The Research Career of Oswald T. Avery,” Historical Studies in the Physical and Biological Sciences 24 (1993): 1-40.


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the Institute. Fearful that the eager investigators would stray from the bedside

in their quest for even more basic knowledge, Cole tried to reassure his

audiences that there was no great danger: hospital-based research would not

become too involved so as to compromise patient care.150 This ethical posture

followed a 1910 press release by the Board of Directors that once more forcefully

asserted: “It should be clearly understood at the outset that this hospital would

have no right, and does not expect, to take any liberties with its patients in this

respect.”151

The success of clinical management required skillful and abundant nursing

support. Cole was not only responsible for all medical staff appointments but

also exercised oversight over other departments such as nursing and

housekeeping. Multiple investigations demanded frequent testing and sampling of

specimens. Around-the-clock monitoring required more night nurses and a higher

ratio per patient. Intelligent nursing observations and reports became an

essential part of the comprehensive tracking of patients. Nurses needed to be

informed and involved in the research projects. They were usually also the best

intermediaries in communicating with the patients and their families. According

to Robinson, however, Cole himself remained more devoted to his own research

laboratory work, delegating much of the administration to his resident physicians

who learned to exercise their own initiative and judgment.152 For more than

150 Cole, The Modern Hospital, p. 128. 151 NY Sun, Oct 18, 1910. 152 Robinson, p. 99.


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twenty years, Cole made sure that clinical inquiries at the Rockefeller Hospital

would not only respect good clinical practices but also fulfill the requirements of

quality biomedical research.153

Perhaps inspired in part by the Franco- German War of 1870, the

employment of war metaphors began in earnest with the advent of bacteriology.

Fighting those deadly germs that “invaded” human bodies became a central

quest in the rise of scientific medicine. “Research,” Cohn dramatically declared,

meant “piercing Nature’ secret armor.”154 Physician-researchers were often

portrayed as the new “scientific soldiers” equipped with microscopes and test

tubes, ready to aggressively battle the enemy. “Mankind is now in face of

enemies which are not localized...carried all over the habitable globe,” wrote

Charles Eliot in 1906.155 War against disease implied a vigorous and continued

engagement that could only end in total victory.156 In an unguarded moment and

perhaps prodded by rival scientists and antivivisectionists, Flexner himself had

sounded a hopeful note by boasting in 1911: “we have already discovered how to

prevent infantile paralysis.”157 Newsmen responded, calling him “one of the real

saviors of the race, fighting tooth and nail and night and day to conquer the

153 Cole, Forschungsinstitute, p. 492. 154 Alfred E. Cohn, No Retreat From Reason, and Other Essays, New York: Harcourt, Brace, 1948, pp. 135-6 155 Charles W. Eliot, “The Future of Medicine,” Science 24 (Oct 12, 1906): 450. 156 Scott L. Montgomery, “Codes and Combat in Biomedical Discourse,” Science as Culture 2 (1991): 341-390. 157 NY Times, Mar 9, 1911.


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diseases which afflict humanity.” 158

Therefore, as polio staged its yearly epidemic outbreaks, all eyes in New

York became trained on the Rockefeller Institute and Flexner’s experimental

work on inoculated monkeys. The serum against cerebrospinal meningitis was

deemed superior to a number of chemical agents and statistically reduced the

mortality from this disease.159 Like Cole’s problem with multiple types of

pneumococcus bacteria, Flexner’s challenge was to produce highly specific

antisera and test them for best results. Could there be soon a specific weapon to

cure polio? Would it be a “javelin”--another serum containing antibodies--or

better yet, a stick of “dynamite,” a chemical germ destroyer like Salvarsan?

To deflect the growing frustrations, Flexner cited the employment of new

diagnostic methods that were already leading to preventive measures and

decreased mortality from the disease. Moreover, it was unfair to tell the public

about ongoing investigations; such statements would likely feed unnecessary

expectations. In fact, the Rockefeller Scientific Board sought to control the news

and was cautious about any claims of discovery. With regard to the conquest of

disease, Flexner objected to the goal of “elimination;” no such predictions were

in order. “There is fighting all along the line,” he was quoted in 1912.160

A year later, the Institute’s director remarked that the poliovirus was

extremely small but its successful inoculation in rhesus monkeys was definitely a 158 NY Times, Jan 24, 1912. 159 S. Flexner and H.L. Amoss, “Chemical Versus Serum Treatment of Epidemic Meningitis,” J. Exper. Med. 23 (May 1, 1916): 683-701. 160 NY Times, Jul 21, 1912.


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step forward.161 Yet stepping into the unknown was fraught with unexpected

hurdles. By the summer of 1916, Flexner was experiencing a shortage of

monkeys, imported from the Philippines.162 As the number of polio cases rose to

new heights, one of his colleagues, Samuel J. Meltzer, proposed the use of

intraspinal injections of a adrenalin solution every six hours for four days,

claiming it would arrest paralyses and “may save lives.”163 The treatment was

also based on experiments conducted on infected monkeys and thus attracted

wide attention, to the chagrin of Flexner who continued to promote his own

serum. This therapeutic competition led to confusion and frustration:

Rockefeller’s millions and his “medical pirates” were assailed and held

responsible for corrupting men and microbes while causing hysteria and

hardships.164 A citizens’ revolt in Oyster Bay charged that philanthropists like

Rockefeller and Carnegie were “actuated by a desire to return a small measure

of god for the millions which they have extorted from the common people.”165

Even an editorial in the New York Times had concluded, “The help has not been

great.”166

161 NY Times, Oct 2, 1913. 162 NY Times, Jul 6 and 7, 1916. 163 Editorial, New York Medical J.104 (1916): 221. See also NY Times, Jul 14, 1916. 164 NY Times, Aug 29, 1916. 165 Minutes, Oyster Bay Town Council, meeting 28 August 1916. For details, Guenter B. Risse, “Revolt Against Quarantine: Community Responses to the 1916 Polio Epidemic, Oyster Bay, New York, Transactions & Studies of the College of Physicians of Philadelphia 14 (1992): 23-50. 166 NY Times, Aug 8, 1916.


61

To this day, institutional culture determines the attitudes and ethical

behavior of its investigators and staff. At the beginning of the century, Osler and

others sought to impose limits on “justifiable” human experimentation: research

needed to be conducted solely for the direct benefit of the patient. At the

Rockefeller Hospital, the reduced size of the collective of physician/scientists

facilitated successful mentoring but it is still unclear how much protection was

given to research subjects. Periodic official declarations sought to preserve the

public trust. Yet, many of the risks remained unknown before and after the

experiments were launched. Transgressions, Osler declared in a 1907 address to

the Congress of American Physicians and Surgeons, would “instantly snap the

sacred cord which binds physician and patient.”

For the next decades, this bond more or less survived, grounded in mutual

trust and expectations based on a model where there was an “almost instinctive

attitude toward the doctor of respect and confidence.” The public believed that

beneficence would guide the conduct of their physicians; they should be

empathetic and determined to place patient welfare above their own

professional interests. Physicians, in turn, trusted patients to comply and support

all medical efforts since they carried the promise of lessening suffering, curing

disease and saving lives. Yet, the demise of the great clinicians endowed with

much art but deficient in science stirred fears that the vaunted “sympathetic

touch” was vanishing, replaced by what was termed “scientific heartlessness.”

Physicians, in turn, were beginning to blame patients for vanishing faith and

impatience in their dealings with medical professionals. “We have been trying


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the last years to teach them a smattering of medicine and have unfortunately

encouraged them to look for quick results in treatment,” bemoaned one

academic in the 1920s.167 One of the Hospital’s staff members, Francis W.

Peabody, addressed the topic in a famous talk to Harvard medical students. “The

Care of the Patient” resonated with the medical profession of its day and

became one of the most quoted articles in the medical literature. Peabody was

emphatic in his belief that the art and science of medicine were not antagonistic

but supplementary, and that an “intimate personal relationship between

physician and patient” was central to the success of medical practice. He was

especially aware of the depersonalizing aspects of hospital practice, urging

empathy and coining the now famous phrase “the secret of the care of the

patient is in caring for the patient.”168

Although mostly unarticulated, the clinical relationship at the Rockefeller

Hospital could be described as “paternalistic.” Doctors knew best. In hospitals

populated by sick indigents, patients were considered “fair game” for those

investigating and learning about disease. For more than 150 years, there had

been an implied social contract: in the very act of accepting hospitalization,

patients had usually consented to an institutional management determined by

medical professionals and presumably administered with the purpose of

167 Guenter B. Risse, “Once on Top, Now on Tap: American Physicians View Their Relationships with Patients, 1920-1970,” in Responsibility in Health Care, ed. G.J. Agich, Dordercht, Holland: Reidel Publishing Co., 1982, pp. 23-49. 168 Francis W. Peabody, “The Care of the Patient, Journal of the American Medical Association 88 (1927): 877-882. For analysis, T.F. Williams, “Cabot, Peabody, and the Care of the Patient,” Bulletin of the History of Medicine 24 (1950): 462-481.


63

improving their condition. Access to hospital wards and patients for purposes of

investigation by outside physicians were common, achieved as part of what was

deemed professional courtesy. These fears prompted the Rockefeller Hospital

Board to issue the statement that “the Hospital would have no right and does not

expect to take any liberties with the patients.” Nevertheless, to achieve near

laboratory conditions, patients would be under complete control of investigators.

No interference with the march of science would be tolerated.

A case report in Oswald Avery’s 1917 monograph provides a glimpse into some

of the rhetoric and reality. A 22 year-old male student admitted to the

Rockefeller Hospital on January 8, displayed all the cardinal symptoms of left

lower lobe pneumonia. Even before sputum and blood tests certified the

presence of pneumococci type I. the patient received his first dose of anti

pneumococcal serum. Unfortunately subsequent injections caused “troublesome”

allergic reactions, including dyspnea, cyanosis, and vomiting. Although

temporarily suspended, the serum injections resumed, eventually causing a full-

fledged case of serum disease with fever, persistent swelling and itching, as well

as joint pains while the patient convalesced from his pneumonia until his

discharge on February 7. “In any case he recovered,” wrote Avery, ”and while

the symptoms due to the serum were somewhat distressing, they were justified

when the results in the whole series of cases is considered.”169

Flexner’s concern for institutional reputation and awareness of the perceived

risks involved in experimentation with patients ultimately compromised both

169 See Avery, Acute Lobar Pneumonia, pp. 80-83.


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laboratory and clinical research. De Kruif, a trained scientist, was equally harsh

in his judgment of Cole’s investigations concerning the use of his serum to treat

pneumonia patients. Giving the remedy to all of them without employing

controls failed to elucidate is efficacy. To avoid hurting patients, all such

experiments were nonsensical. As virtual co-author of Arrowsmith, De Kruif has

Dr. Gottlieb/Flexner demand that his pupil employ his anti-plague serum on only

half of the patient population, using the other as control. This arbitrary and

random determination was felt to be essential for determining its value and thus

perhaps conquer plague forever, but its potential cruelness inhibited application.

When Arrowsmith expresses doubts about using sufferers as pure objects of an

experiment, Gottlieb challenges: “Want to be a miracle man or a scientist?” 170

To be a true experimentalist, Arrowsmith “must harden his heart and keep clear

his eyes.”171 However, the use of randomized human controls remained a morally

unacceptable alternative for members of the Rockefeller Institute and Hospital.

Yet, even without human controls, ambiguities and potential for harm

remained, exacerbated by the new research imperatives. Like all sera derived

from immunized animals and even humans, their administration could cause

severe allergic reactions, even anaphylactic shock. Cole and Peabody resisted

the need for formal consent, assuming that patient cooperation was sufficient.

To prevent distrust, however, Cole sought to address widespread public

concerns: “The methods employed have been those of clinical investigation, not

170 Sinclair, Arrowsmith, p. 327. 171 Ibid, p. 361.


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human experimentation,” insisting “every patient has been safeguarded from

anything which might be to his detriment.”172 Only controlled animal

experimentation was the proper way to illuminate the problems of human

medicine. Cole concluded that one of the hospital staff’s most cherished beliefs

was that “even if experimentation on patients were morally justifiable, which it

is not, the increase in knowledge derived thereby would be negligible.”173 A

decade later, Cole reiterated his strong belief that medical research was not

opposed to the highest humanitarian motives or the best medical treatment.”174

For the privilege of being cared for at this prestigious institution, evidence

suggests that at least some patients reciprocated by cheerfully accepting the

responsibility of becoming research subjects for their own benefit or that of

others. Professional moral certainty left ethical issues unanswered. To uphold

the covenant, there was considerable latitude about what kind of information

physicians provided. But, could the patients understand what was at stake?

Children simply followed the wishes of their concerned but trusting parents.

Could investigations actually become detrimental to their condition? As one

anthropologist interviewing physician-investigators from that era discovered,

patient rights and choice, autonomy and risk, had yet to be explicitly articulated

as important human values. Truth telling was considered a double-edged sword

and the practice of “benevolent deception” widespread.

172 Cole, Forschungsinstitute, p. 492 173 Ibid. 174 Cole, The Modern Hospital, p. 127.


66

At the Hospital, the patient–physician/investigator relationship would

have benefited from the higher social status and the extended stay of many

patients. There were no institutional or financial pressures for early discharges;

everyone could be thoroughly evaluated. However, scientific detachment and

accurate judgment precluded excessive intimacy. Nevertheless, a few

expressions of altruism and gratitude from patients suggest the occasional

development of true partnerships. Since disease was their common enemy,

resident physicians and patients were expected in military terms to join forces,

forge an alliance, and become comrades in the ongoing fight for survival. In a

letter to Rockefeller Jr., the daughter of a deceased patient expressed her

“intense feelings of appreciation” that her mother had been of service to

humanity before her life ended in the hospital, “She derived profound

satisfaction from the knowledge that in her way she was contributing,” wrote

the daughter.175

Epilogue

Together the Rockefeller Research Institute and Hospital became a unique

platform linking the biological with the medical and thereby establishing the

foundations of a genuine biomedicine. Even before his formal appointment as

director, Simon Flexner had written in 1902 “we shall be closely watched by the

hospitals in this country as well as by the general profession at home and abroad.

Everything will lead to bring the Institute and Hospital into prominence; their

175 Corner, A History, p 281.


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close association, the ideals for which they stand. We shall be without hindrance

and shall have the world’s experience gathered at first hand as a heritage.”176

Reflecting on the first two decades of experience at the Rockefeller

Hospital, Cole pointed out what was probably the greatest bequest of the

institution and its investigative mission: “developing the inquiring attitude of

mind” of medical practitioners. The unique melding of clinical investigation and

medical care shaped the character and service of the establishment’s unique

personality. Henceforth, American physicians would no longer be content to

simply base their professional credentials on superior bedside skills. According to

Cole, “the man engaged in the study of disease has an academic right to go just

as deeply into the study of the fundamental nature of the disease as his training

will warrant.”177 Henceforth, clinician-investigators preferred to portray

themselves as individuals who strived to research and understand the causes and

basic mechanisms involved in the diseases that afflicted their charges before

seeking to alleviate or cure based on that knowledge. Emphasis was on the

former, in tandem with more precise diagnoses achieved with the aid of

laboratory findings.

Among early achievements was the aforementioned use of oxygen and

serotherapy for certain types of pneumonia, although less favorable statistics

from subsequent post WWI trials exposed reliance on case series without

176 Flexner to Herter, Jan 6, 1902, Rockefeller Institute files, quoted in Corner, A History, p. 88. 177 Ahrends, The Birth, p. 551.


68

controls.178 The serological treatment of meningococcal meningitis,179 as well as

dietary management of diabetes were widely employed thanks to a better

understanding of the role played by the pancreatic insulin-producing Langerhans

cells. Moreover, both Rockefeller institutions played important roles in studying

poliomyelitis, late stage syphilis, nephritis, and bronchial asthma. On the

diagnostic side, the employment of electrocardiography marked a milestone in

our understanding of cardiac physiology and physiopathology. During this entire

process, physicians raised questions and quantified a wide spectrum of

biochemical phenomena establishing new normal values as well as early signs of

multiple ailments.180

In his commencement address to the graduating class at Yale Medical

School in June 1911, Walter B. Cannon, professor of physiology at Harvard,

sought to promote careers in medical research, framing them as exciting

adventures and explorations that would propel its practitioners beyond the

existing but limited frontiers of knowledge, thus serving present and future

generations afflicted with deadly scourges. Besides curiosity, imagination, and

dedication, would-be medical scientists needed to display indifference towards

money. Although investigators would be removed from the immediate distress of

sick people, they could still experience profound satisfaction: “the greatest

178 Podolsky, The Advent, pp. 18-19. 179 S. Flexner and J.W.Joblin, “An Analysis of Four-Hundred Cases of Epidemic Meningitis With Antimeningitis Serum,” J. Exper. Med 10 I1908): 690-733. 180 S. Flexner, Twenty-five Years of Bacteriology: A Fragment of Medical Research,” Science 52 (1920): 615-632.


69

compensation for the truth seekers is the discovery of the truth.”181 The key was

to find sponsors willing to finance such biomedical investigations providing free

time for thoughts and experiments.

By the 1920s, a cadre of new full-time academic physicians emerged,

trained in both the basic sciences and care of patients. Reviewing the impact of

the Rockefeller Hospital in the 1950s with the help of statistics, Robinson

concluded that members of the early medical staff went on to occupy some of

the most prestigious and influential academic posts in medicine in the US and

abroad, especially England and China. “I have felt that the Hospital might play

some part in bringing about this changed conception of internal medicine,” Cole

had written.182 Infused with this aura of scientific dignity, internal medicine

became one of the most coveted specialties. It’s no exaggeration to say that

both Rockefeller enterprises were responsible for dramatically bolstering the

cultural authority of American physicians, many equipped with both MD and PhD

degrees.183

Yet, the Rockefeller Hospital legacy remains ambiguous. While the original

hopes for the conquest of particular diseases were only partially realized, the

contributions of the Hospital were more subtle and general in nature. The

research illuminated a number of basic physiological mechanisms and promoted

181 Walter B. Cannon, “The Career of the Investigator,” Science 34 (Jul 21, 1911): 70. 182 Ahrends, The Birth, p. 550. 183 See article “Medicine at Rockefeller Hospital” in Time Magazine, May 24, 1937.


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advances in the biology of microbes and viruses as well as immunochemistry.184

De Kruif had already observed in the 1920s that lavish funding per se would not

lead to major scientific breakthroughs. Citing the example of cancer, “mortal ills

were reluctant to fall before an organized onslaught from men, money and

materials.”185 Flexner, for his part, reiterated that the very air of the hospital

fostered clinical research. He was emphatic that investigators remain in hospitals

and should not migrate to general laboratories.186 Cole continued to assert that

scientific investigations would lend prestige to local hospitals and widen their

appeal as serving “all mankind.”187 Among his proudest contributions was the

establishment of a brand new medical school with its affiliated hospital at the

University of Chicago in 1927.

In the final analysis, the Rockefeller Hospital became a difficult model to

emulate. The institution had a very limited number of beds and a small, full-time

staff; it was under no obligation to admit emergencies The institution operated

in total financial independence based on endowments and performed no

academic teaching functions beyond the training of its own house staff.

Moreover, investigators determined the parameters of their research and solely

admitted patients suffering from diseases targeted for study. Like all other

hospitals, Rockefeller clinical scientists eschewed the use of control subjects in 184 Saul Benison, “The Development of Clinical Research at the Rockefeller Before 1939,” in Trends in Biomedical Research, 1901-1976, Proceedings of the 2nd Annual Rockefeller Archives Center Conference, Dec 10, 1976, pp. 35-45. 185 De Kruif, The Sweeping Wind, p. 21. 186 Flexner, Evolution and Organization of the University Clinic, Oxford, p. 37. 187 Cole, “The Modern Hospital,” p. 127.


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testing their therapeutic agents, a practice that only began to gain wider

acceptance after WWI.

As early as 1910, Cole had predicted that the Rockefeller Hospital would

play an important part in the reorganization of American medicine, especially

among academic medical centers. In 1913, the New York Times commented:

“the princely gifts to medicine will place fresh companies of research workers

above all need of material things at posts where they may aid sick humanity in

the present and in future generations.”188 In the 1920’s, Peabody proclaimed

that leading hospitals owned their reputation from sponsoring research. In fact, a

number of prestigious institutions began setting up particular wards solely

devoted to clinical investigation. Among them were the Metabolic Ward at

Bellevue (1913), the Thorndike Laboratory at Boston City (1923), Ward 4 Edsall,

at Massachusetts General (1925) and the Osler 5 facility at Johns Hopkins (1930).

As these events unfolded, Cole spoke of a shift in medical mentality. Emerging

was a new curiosity and desire for understanding the basic biological roots of

diseases that could improve clinical management and achieve better therapeutic

results.189 Indeed, the presence of younger physician/researchers came to

bestow a progressive image of cutting-edge research, up=to-date technology,

and improved medical care to university-affiliated hospitals that survives into

our own days. Many of us still check their annual ratings and seek them out for

health care.

188 NY Times, Oct 25, 1913. 189 Cole, Forschungsinstitute, p.493.


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For Cole, hospitals “depended upon the ability and energy of the

physicians working within its walls. Although organization and equipment offered

opportunities, success really depended “upon the character of the men who are

attracted to join its activities and upon the breadth of the spirit of service that

pervades its atmosphere.”190 Cole lobbied for protection and relief from an

excess of routine duties, especially the “exaction of private practice.” Research

in medicine was not antagonistic to the highest humanitarian motives or the best

outcomes; quite the reverse was true.191 Persistence of the Rockefeller-inspired

and hospital-based investigational ethos remains ubiquitous. When I joined the

Cole’s University of Chicago Hospitals and Clinics in 1962, following completion

of my residency in internal medicine, one distinguished academic confided: “I

wish we could shut the doors of our hospital to ordinary patients for the next

fifteen years and just do research.” He added: “I do not wish to waste my time

with routine practice; this is such an exciting time for medical discovery. Turn

the ambulances around and send them to other hospitals.”192

190 Cole, Modern Hospital, p.130. 191 Ibid, p. 127. 192 Personal communication.

a hospital for all mankind': clinical investigation at the hospital of the rockefeller medical...

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